Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: roles of antioxidation, anti-inflammation, and pro-survival.
Lu Shan,Wu Daoshun,Sun Guibo,Geng Funeng,Shen Yongmei,Tan Jin,Sun Xiaobo,Luo Yun
Pharmaceutical biology
Kangfuxin (KFX) is widely used for the treatment of gastric and duodenal ulcer; however, more research is needed to determine the protective mechanisms of KFX in ameliorating gastric ulcer. To investigate the efficacy and potential mechanism of Kangfuxin liquid (KFX) in water-immersion and restraint stress (WIRS)-induced gastric ulcer. Seventy rats were randomly divided into seven groups ( = 10) as follows: the control group (normal saline, i.g.), the model group (normal saline, i.g.), the KFX groups (2.5, 5 and 10 mL/kg, i.g.), the omeprazole group (20 mg/kg, i.p.) and Sanjiuweitai Granules group (1850 mg/kg, i.g.). The WIRS model was applied to induce stress ulcers after 7 days of drug administration. Afterwards, rats were sacrificed at 10 h induced by WIRS. Pre-treatment with KFX (5,10 mL/kg) could effectively reduce the area of gastric ulcers and improve the pathological changes of ulcerated tissue. Moreover, KFX (5,10 mL/kg) increased the prostaglandin E2 (52%) and cyclooxygenase-1 (30%) levels, and improved malondialdehyde (54%), superoxide dismutase (58%), catalase (39%), and nitric oxide (11%) and TNF-α (9%), IL-6 (11%), MMP-9 (54%) and MMP-2 (53%) of ulcer tissue. Furthermore, pre-treatment with KFX dramatically increased IGF-1, PTEN, and Akt protein expression. Our results suggest that KFX has protective effects on WIRS-induced gastric ulcer via inflammatory reactions, oxidative stress inhibition, and pro-survival action, which were the results of activating the IGF-1/PTEN/Akt signalling pathway. Our results provide evidence of KFX for treating gastric ulcer.
10.1080/13880209.2019.1682620
Temperature-sensitive hydrogel for rectal perfusion improved the therapeutic effect of Kangfuxin liquid on DSS-induced ulcerative colitis mice: The inflammation alleviation and the colonic mucosal barriers repair.
Xue Pengpeng,Wang Lifen,Xu Jiawei,Liu Jiayi,Pan Xiaohong,Zhao Yingzheng,Xu Helin
International journal of pharmaceutics
Kangfuxin liquid (KFX) is a Chinese medicine extracted from Periplaneta americana dried worms, which presented the bioactive functions of anti-inflammation and promoting the gastrointestinal mucosal barriers repair. But the low availability of KFX exposed to the distal colon affects its therapeutic effect on ulcerative colitis. Herein, an in situ hydrogel containing KFX was designed by using temperature-sensitive poloxamer 407 (P-407) as material for rectal administration. Three KFX-P formulations with different P407 concentrations (17%, 20% and 25%) were designed and screened by detecting the gelation time, gelation temperature and mechanical strength of hydrogel. P407 in these formulations was able to be completely dissolved in KFX at 4 ℃ and then was in situ gelled at 37 ℃ to form a semisolid hydrogel. Moreover, the gelation time, the gelation temperature and the mechanical strength of KFX-P hydrogel are highly dependent on P407 concentration. With P407 concentration increasing, both the gelation time and gelation temperature of KFX-P accordingly decreased and the gelation temperature range becomes narrowed; while the mechanical strength increased. KFX-P-20% displayed the moderate gelation temperature (28-30 ℃), the short gelation time (26 s) and the moderate mechanical strength (G' = 4.2 × 10 Pa), which was chosen for animal study. Thereafter, ulcerative colitis mice model (UC) was established by dextran sulfate sodium (DSS) and the therapeutic effect of KFX-P on UC was evaluated by inflammation symptoms relief, colon length, colonic MPO level and colonography. After rectal administration of KFX or KFX-P, the symptoms including diarrhea and hematochezia (DAI scores), weight loss and spleen swelling were significantly hindered. Meanwhile, the colonic MPO level in these groups was significantly decreased in comparison with PBS treatment. But the therapeutic effect of KFX-P was better than KFX. Besides, the morphology and mucosal barrier of colon were evaluated by HE staining, ZO-1 and claudin-5 staining. The mucosa epithelium layer, crypt, muscle layer mucosa and submucosa were also well repaired after KFX-P treatment. The strong fluorescence of ZO-1 and claudin-5 were uniformly distributed along the whole epithelial mucosa after KFX-P treatment, indicating the effective repairing of the colonic mucosal barrier. Collectively, the temperature-sensitive KFX-P for rectal delivery could effectively promote the repair of the colon mucosal barrier and inhibit the colonic inflammation in DSS-induced mice, which may be a potential strategy for UC treatment.
10.1016/j.ijpharm.2020.119846
To Explore the Protective Mechanism of PTEN-Induced Kinase 1 (PINK1)/Parkin Mitophagy-Mediated Extract of Periplaneta Americana on Lipopolysaccharide-Induced Cardiomyocyte Injury.
Li Jie,Shi Wei,Zhang Jun,Ren Liqun
Medical science monitor : international medical journal of experimental and clinical research
BACKGROUND Sepsis is defined as a systemic inflammatory response syndrome caused by an infection (suspicious or confirmed). Its essence is inflammatory mediators and cytokines mediated by host immune response. The present study aimed to investigate the role of Periplaneta americana extracts (XML) on PTEN-induced kinase 1 (PINK1)/Parkin mediated mitophagy in cardiomyocyte injury by sepsis. MATERIAL AND METHODS H9C2 cells were cultured and transfected with Mdivi-1 and Atg7 siRNA. The cell viability and drug toxicity were detected using Cell Counting Kit-8 assay. ELISA (enzyme-linked immunosorbent assay) was used to assess cardiac injury factors and inflammatory factors. Fluorescence levels of LC3 were detected using immunofluorescence assay. Then, the protein and mRNA expression levels were analyzed using western blot and qRT-PCR. Intracellular adenosine triphosphate (ATP) levels were measured using an ATP kit. Finally, flow cytometry was used to detected apoptosis. RESULTS The result showed that XML significantly increase cell viability in H9C2 cells. Compared with XML+LPS (lipopolysaccharide) group, the level of cTNI, CK-MB, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α was significantly upregulation in LPS+XML+Mdivi-1 or LPS+XML+Atg7 siRNA group. In addition, the release of LC3 was significant decreased. The protein and mRNA expression of PINK1, Parkin, Nix, Beclin-1 was significantly increased, but decreased expression of Mitofusin1, Mitofusin2, Opa1, Drp1, and P62 in LPS+XML+Mdivi-1 or LPS+XML+Atg7 siRNA groups. More importantly, we found that cell apoptosis was induced by Mdivi-1 and Atg7 siRNA. CONCLUSIONS The study provided evidence that XML regulated the process of LPS-induced cardiomyocyte injury through mitophagy by the PINK1/Parkin pathway.
10.12659/MSM.912980
The effects and mechanism of Kangfuxin on improving healing quality and preventing recurrence of gastric ulcer.
Tian Ming,Dong Jiaoyun,Wang Zhengting,Lu Shuliang,Geng Funeng
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
This study investigated the gastroprotective effects and possible mechanism of Kangfuxin (KFX), an ethanol extract of Periplaneta americana L. (Dictyoptera; Blattidae), on improving healing quality and preventing recurrence of gastric ulcer. The effects of KFX were investigated in patients treated with endoscopic submucosal dissection (ESD), gastric ulcer animal model, and rat gastric mucosal cells and fibroblasts. Moreover, the relationship between KFX and p38/NF-κB pathway were explored both in vivo and in vitro. In patients, KFX exhibited protective effects against gastric ulcers and resulted in a decrease in the CD3 expression. In vivo animal experiments confirmed that KFX accelerated ulcer healing by promoting neovascularization (increased CD34 expression), suppressing inflammation (decreased interleukin-1β (IL-1β), myeloperoxidase (MPO), tumor necrosis factor α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and IL-8 expression), and enhancing growth factor expression, including the epidermal growth factor receptor (EGFR) and hepatocyte growth factor (HGF). In vitro experiments demonstrated that treatment with 10% KFX rat serum decreased IL-1β, IL-1Ra, SIL-1RAP, TNF-α, and ICAM-1 expression in rat gastric mucosal cells or fibroblasts and increased IL-1R expression compared to that in the group treatment with 10% normal rat serum. Furthermore, KFX inhibited the activation of p38/NF-κB pathway both in vivo and in vitro. In conclusion, KFX treatment could effectively improve healing quality and prevent gastric ulcer recurrence, which might be attributed to neovascularization, suppressed inflammation, and enhanced growth factor expression. The p38/NF-κB pathway may be one of important mechanism to mediate the effects of KFX.
10.1016/j.biopha.2021.111513
The Effect of Xinmailong Infusion on Sepsis-Induced Myocardial Dysfunction: a Pragmatic Randomized Controlled Trial.
He Jianzhuo,Zhao Xujie,Lin Xinfeng,Yang Zhixu,Ma Mingyuan,Ma Li,Liang Qun,Li Lan,Ye Yong,Wen Zehuai,Zhang Zhanlin,Zhang Minzhou,Guo Liheng
Shock (Augusta, Ga.)
ABSTRACT:Sepsis-induced myocardial dysfunction (SIMD) contributes significantly to cardiovascular dysfunction during septic shock. We aimed to evaluate the potential role of Xinmailong injection (XMLI), a polypeptide medicine extracted from Periplaneta americana, in reversing the progression of myocardial damage to SIMD in sepsis patients. This was a multicenter, randomized, double-blind, parallel-group trial. We recruited all patients consecutively admitted to intensive care units (ICUs) who were aged 18 to 85 years old and met the sepsis 3.0 criteria. The primary outcome measure was the incidence of sepsis-induced myocardial dysfunction while in the ICU. Of the 192 patients, 96 were assigned to the treatment group, and 96 to the control group. Subsequently, 41 patients [41/96 (42.7%)] in the XMLI group and 61 patients in the placebo group [61/96 (63.5%)] were confirmed to have diastolic dysfunction on the fifth day (D5). The incidence of diastolic SIMD was significantly different between the two groups (P = 0.004). There were 36 deaths in the two groups during the 28-day follow-up, with a general mortality rate of 18.8% (36/192). The 28-day mortality rates were not significantly different between the groups (P = 0.45). However, the brain natriuretic peptide (BNP) plasma concentration trends on D0, D2, and D5 significantly differed between the two groups (P = 0.049). In septic patients, XMLI decreased the occurrence rate of diastolic SIMD more effectively than the placebo. The improvement in serum BNP concentration was also greater in the XMLI group. XMLI may, therefore, effectively and safely improve cardiac function in patients with sepsis.
10.1097/SHK.0000000000001592
Clock-controlled arylalkylamine N-acetyltransferase (aaNAT) regulates circadian rhythms of locomotor activity in the American cockroach, Periplaneta americana, via melatonin/MT2-like receptor.
Kamruzzaman A S M,Hiragaki Susumu,Watari Yasuhiko,Natsukawa Takashi,Yasuhara Akie,Ichihara Naoyuki,Mohamed Amr A,Elgendy Azza M,Takeda Makio
Journal of pineal research
Melatonin (MEL) orchestrates daily and seasonal rhythms (eg, locomotion, sleep/wake cycles, and migration among other rhythms) in diverse organisms. We investigated the effects of pharmacological doses (0.03-1 mM) of exogenous MEL intake in the cockroach, Periplaneta americana, on locomotor activity. As per os MEL concentration increased, cockroach locomotor rhythm in light-dark (LD) cycles became more synchronized. The ratio of night activity to 24-h activity increased and the acrophase (peak) slightly advanced. MEL application also influenced total activity bouts in the free-running rhythm. Since MEL slightly influenced τ in the free-running rhythms, it is not a central element of the circadian pacemaker but must influence mutual coupling of multi-oscillatory system components. Arylalkylamine N-acetyltransferase (aaNAT) regulates enzymatic production of MEL. aaNAT activities vary in circadian rhythms, and the immunoreactive aaNAT (aaNAT-ir) is colocalized with the key clock proteins cycle (CYC)-ir and pigment-dispersing factor (PDF)-ir These are elements of the central pacemaker and its output pathway as well as other circadian landmarks such as the anterior and posterior optic commissures (AOC and POC, respectively). It also partially shares immunohistochemical reactivity with PER-ir and DBT-ir neurons. We analyzed the role of Pamericana aaNAT1 (PaaaNAT1) (AB106562.1) by injecting dsRNA . qPCR showed a decrease in accumulations of mRNAs encoding PaaaNAT1. The injections led to arrhythmicity in LD cycles and the arrhythmicity persisted in constant dark (DD). Continuous administration of MEL resynchronized the rhythm after arrhythmicity was induced by dsRNA injection, suggesting that PaaaNAT is the key regulator of the circadian system in the cockroach via MEL production. PaaaNAT1 contains putative E-box regions which may explain its tight circadian control. The receptor that mediates MEL function is most likely similar to the mammalian MT2, because injecting the competitive MT2 antagonist luzindole blocked MEL function, and MEL injection after luzindole treatment restored MT function. Human MT2-ir was localized in the circadian neurons in the cockroach brain and subesophageal ganglion. We infer that MEL and its synthesizing enzyme, aaNAT, constitute at least one circadian output pathway of locomotor activity either as a distinct route or in association with PDF system.
10.1111/jpi.12751
Ento-A alleviates DSS-induced experimental colitis in mice by remolding intestinal microbiota to regulate SCFAs metabolism and the Th17 signaling pathway.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by changes in the metabolism of short chain fatty acids (SCFAs), dysregulation of gut microbiota, and an imbalance of Treg/Th17. Herein, we explore the effects of the Ento-A (an alcohol extract of Periplaneta americana L.) on a mouse model of UC. First, a chronic and recurrent UC model was constructed in BALB/c mice by 2.2% DSS administration. UC mice were continuously treated for 14 days with Ento-A (50, 100, 200 mg/kg, i.g.) or a negative control. Ento-A alleviated many of the pathological changes observed in UC mice, such as body weight loss, disease activity index, changes in colon length, and colonic mucosal damage index. Ento-A also decreased levels of proinflammatory cytokines (IL-1β, IL-6, IL-17A, and TNF-α), increased levels of anti-inflammatory cytokines (IL-10 and TGF-β1) and repaired the intestinal mucosal barrier. Additionally, Ento-A regulated the proportions of Th17 cells, and Treg cells in mesenteric lymph nodes harvested from treated mice (as assessed by Flow cytometry), and the expression levels of IL-17A and Foxp3 in colon (as assessed by immunohistochemistry). 16 S rRNA gene sequencing revealed that Ento-A regulated gut microbiota. GC-MS analysis demonstrated that Ento-A also restored SCFAs content in the intestinal tract. Finally, transcriptomic analysis revealed that Ento-A regulated the IL-17 signaling pathway. In summary, Ento-A regulates the diversity and abundance of intestinal flora in UC mice, enhancing the secretion of SCFAs, subsequently regulating the IL-17 signaling pathway, and ultimately repairing the intestinal mucosal barrier.
10.1016/j.biopha.2023.115985
extract ameliorates lipopolysaccharide-induced liver injury by improving mitochondrial dysfunction via the AMPK/PGC-1α signaling pathway.
Shi Wei,An Li,Zhang Jun,Li Jie
Experimental and therapeutic medicine
(PA) extract acts clinically as a therapeutic treatment in various diseases; it enhances liver function in mouse models and mitigates the pathological condition of liver fibrosis. The present study aimed to investigate the role and potential mechanisms underlying the action of the PA extract, xinmailong (XML), in lipopolysaccharide (LPS)-induced liver injury. Following the treatment of AML12 cells with LPS, the content of cytochrome in the cytoplasm and mitochondria, and the level of ATP synthesis were detected using corresponding kits. The relative mRNA expression levels of nuclear respiratory factor 1 and transcription factor A, mitochondrial were investigated using reverse transcription-quantitative (RT-q)PCR analysis. The MTT assay was performed to detect the viability of AML12 cells following treatment with XML, in the absence or presence of LPS. Western blot analysis was performed to determine the expression levels of proteins in the AMP-activated protein kinase (AMPK)/proliferator-activated receptor γ coactivator-1α (PGC-1α) pathway. Following treatment with compound C, an inhibitor of AMPK, the expression levels of inflammatory cytokines were determined using ELISA and RT-qPCR analysis. The levels of oxidative stress-related markers were detected using corresponding kits following treatment with compound C. In addition, TUNEL staining was performed to detect the apoptosis of AML12 cells, and western blot analysis was performed to investigate the expression levels of apoptosis-related proteins. Mitochondrial dysfunction was induced by LPS in AML12 cells. LPS stimulation significantly downregulated the expression of proteins in the AMPK/PGC-1α pathway, which was reversed following treatment with XML. In addition, inflammation, oxidative stress and mitochondrial dysfunction induced by LPS were alleviated by XML in AML12 cells. However, the addition of compound C and XML to LPS-induced AML12 cells resulted in the aggravation of cell injury. Collectively, the results of the present study indicated that XML suppressed mitochondrial dysfunction induced by LPS by activating AMPK/PGC-1α signaling. Thus, the results of the present study may contribute to further understanding of the underlying mechanism via which XML alleviates liver injury.
10.3892/etm.2021.10572
Periplaneta americana extract promotes hard palate mucosal wound healing via the PI3K/AKT signaling pathway in male mice.
Archives of oral biology
OBJECTIVES:This study aimed to investigate the effect of Periplaneta americana extract, a traditional Chinese medicine, on hard palate mucosal wound healing and explore the underlying mechanisms. DESIGN:Hard palate mucosal wound model was established and the effects of Periplaneta americana extract on hard palate mucosal wound healing were investigated by stereomicroscopy observation and histological evaluation in vivo. Human oral keratinocytes and human gingival fibroblasts, which play key roles in hard palate mucosal wound healing, were selected as the main research cells in vitro. The effects of Periplaneta americana extract on cell proliferation, migration, and collagen formation were determined by cell counting kit-8 (CCK-8) assay, Transwell assay, and Van Gieson staining. The underlying mechanism was revealed by RNA sequencing, and results were verified by western blot assay. RESULTS:Stereomicroscopy observation and H&E staining confirmed that Periplaneta americana extract accelerated the healing rate of hard palate mucosal wound (p < 0.001) in vivo. Transwell assay and Van Gieson staining assay showed that Periplaneta americana extract promoted the migration and collagen formation of human oral keratinocytes (p < 0.001) and human gingival fibroblasts (p < 0.001) in vitro. Mechanistically, RNA sequencing and western blot assay demonstrated that Periplaneta americana extract promoted hard palate mucosal wound healing via PI3K/AKT signaling, and the beneficial effects of Periplaneta americana extract were abrogated by the PI3K inhibitor LY294002. CONCLUSIONS:Periplaneta americana extract shows promising effects for the promotion of hard palate mucosal wound healing and may be a novel candidate for clinical translation.
10.1016/j.archoralbio.2023.105856
The protective effect of small peptides from Periplaneta americana on hydrogen peroxide-induced apoptosis of granular cells.
Wang Qin,Fu Rong,Kong Caihua,Liu Kena,Si Huaxin,Sui Shiyan
In vitro cellular & developmental biology. Animal
This study investigates the protective effect of small peptides from Periplaneta americana (SPPA) on hydrogen peroxide (HO)-induced apoptosis of ovarian granular cells. HO was applied to human ovarian granular cells (KGN cell strains). Cell viability was tested by cell counting Kit-8 (CCK-8). Cell apoptosis was tested by flow cytometry, and a cell apoptosis model was established. The model cells were treated with SPPA, and the cell survival rate was monitored using the CCK-8 method. The oxidative stress state of cells was examined using SOD, ROS, MDA, and NO kits. The protein expression levels of SIRT1, p53, and the apoptosis-related gene Caspase3 were measured using Western Blot methodology. Relative to the control group, cell viability declined significantly after the HO treatment only (P < 0.01), while the apoptosis rate increased significantly (P < 0.01). The activity of SOD was weakened significantly (P < 0.01), while the cell levels of ROS, MDA, and NO increased dramatically (P < 0.01). Cell viability dramatically recovered (P < 0.01), and the SOD activity is hugely increased (P < 0.01) after SPPA treatment. In contrast, contents of ROS, MDA, and NO decreased sharply (P < 0.01), and significant dose-response relationships are characterized. Moreover, the HO treatment group showed significantly downregulated expression of SIRT1 (P < 0.01) but significantly upregulated expressions of p53 and Caspase3 (P < 0.01) compared to the control group. Following the SPPA treatment of apoptosis cells, expression of SIRT1 increased significantly, while expressions of p53 and Caspase3 declined significantly (P < 0.01). This study suggests that SPPA inhibits HO-induced human KGN cell apoptosis through antioxidation, and the SIRT1/p53 signal pathway mediates the antioxidation.
10.1007/s11626-021-00586-2
N-containing phenolic compounds from Periplaneta americana with triple negative breast cancer inhibitory activity.
Phytochemistry
Eight previously undescribed compounds comprising pyrrole-2-carboxaldehyde derivatives, namely periplanpyrroles A-D (1-4), spirooxindole derivatives perispirooxindoles A (5) and B (6), and the phenolic compounds periplanetols G (7) and H (8), along with eight known compounds were isolated from the 70% ethanol extract of the whole bodies of Periplaneta americana. Their structures including absolute configurations were unambiguously identified by comprehensive spectroscopic analyses and computational methods. In addition, all compounds were evaluated for their activities against triple negative breast cancer in vitro. The wound healing assay revealed that 7, 9, and 11 significantly inhibit the migration of BT549 and MDA-MB-231 cells. Further observations made in Western blotting experiments showed that 7 could dose-dependently decrease the protein level of vimentin and N-cadherin in MDA-MB-231 and BT549 cells.
10.1016/j.phytochem.2023.113936
Periplanetols A-F, phenolic compounds from Periplaneta americana with potent COX-2 inhibitory activity.
Bai Hong-Fu,Li Yan-Peng,Qin Fu-Ying,Yan Yong-Ming,Wang Shu-Mei,Zhang Hao-Xing,Cheng Yong-Xian
Fitoterapia
Six new compounds, periplanetols A - F (1-4, 6 and 7), a compound isolated from natural origin for the first time (5), and nine known ones (8-16) were isolated from the 70% ethanol extract of the whole bodies of Periplaneta americana. Their structures including absolute configurations were unambiguously identified by comprehensive spectroscopic analyses and computational methods. Biological evaluation toward COX-2 inhibition revealed that compounds 1, 2, and 10 could inhibit COX-2 activity with the IC values of 768.0 nM, 617.7 nM, and 599.5 nM respectively, indicating their potential in developping novel agents against inflammation related disorders.
10.1016/j.fitote.2020.104589
A Schiff base hydrogel dressing loading extracts from Periplaneta Americana for diabetic wound healing.
International journal of biological macromolecules
As a common complication of diabetic patients, the chronic wound of diabetes has a high incidence, expensive treatment, and recurrence probability, which causes long-term negative impacts on patients' daily life. In this study, the hydrogel was formed by Schiff base reaction between oxidized hyaluronic acid (OHA) and carboxymethyl chitosan (CMCS), and the composite hydrogel dressing was prepared by adding the active polypeptides extract of Periplaneta Americana (PAE). By mass spectrometer determined, PAE mainly includes vitellogenins that can trigger an immune response. The composite hydrogel has good swelling properties, proper fluidity, and a regular 3D network structure. The hydrogel has good cytocompatibility and can promote cell proliferation by L929 fibroblast assay. Finally, it was used to evaluate the effect of diabetic wound repair. The results showed that it could effectively promote wound healing, promote tissue and vascular regeneration, inhibit inflammatory factors, and promote the expression of growth factors. The OHA/CMCS/PAE hydrogels would be promising candidates for chronic wound healing applications.
10.1016/j.ijbiomac.2023.123256
Cloning, Expression and Effects of Thymosin on Wound Healing.
Jing Jie,Sun Xiaohong,Zhou Chuang,Zhang Yifan,Shen Yongmei,Zeng Xiaomao,Yue Bisong,Zhang Xiuyue
International journal of molecular sciences
The American cockroach () is a medicinal insect. Its extract is used clinically to promote wound healing and tissue regeneration, but the effective medicinal components and mechanisms are not yet clear. It has been reported that human thymosin beta 4 (Tβ4) may accelerate skin wound healing, however, the role of thymosin (Pa-THYs) is still poorly understood. In the present study, we identify and analyze the DNA sequences of Pa-THYs by bioinformatics analysis. Then we clone, express, and purify the Pa-THYs proteins and evaluate the activity of recombinant Pa-THYs proteins by cell migration and proliferation assays in NIH/3T3 cells. To elucidate the role of Pa-THYs in wound healing, a mouse model is established, and we evaluate wound contraction, histopathological parameters, and the expressions of several key growth factors after Pa-THYs treatment. Our results showed that three THY variants were formed by skipping splicing of exons. Pa-THYs could promote fibroblast migration, but have no effect on fibroblast proliferation. In wound repair, Pa-THYs proteins could effectively promote wound healing through stimulating dermal tissue regeneration, angiogenesis, and collagen deposition. On the molecular mechanism, Pa-THYs also stimulated the expression of several key growth factors to promote wound healing. The data suggest that Pa-THYs could be a potential drug for promoting wound repair.
10.3390/ijms20194932
Signaling pathways of Periplaneta americana peptide resist HO-induced apoptosis in pig-ovary granulosa cells through FoxO1.
Kong Caihua,Su Jingjing,Wang Qin,Liu Kena,Fu Rong,Sui Shiyan
Theriogenology
Granulosa cell apoptosis induced by oxidative stress is an important cause of follicular atresia. Our previous studies found that Periplaneta americana peptide (PAP) decreased HO-induced apoptosis of pig-ovary granulosa cells (PGCs) through FoxO1. The aim of this study is to investigate the signaling pathways involved in PAP resistance against HO-induced apoptosis of PGCs. PGCs obtained from the follicles of non-estrous Duroc × Landrace × Yorkshire gilts (5 months old, 50-55 kg) were treated with HO and PAP, or together with inhibitors against PI3K and JNK, and then collected for ROS levels and SOD activities detection, TUNEL staining, qRT-PCR, western blotting, immunofluorescence or coimmunoprecipitation. Results showed that the increased ROS levels and decreased activities of SOD caused by HO stimulation were reversed by PAP. Additionally, PAP downregulated the differential abundance of mRNA of Bax and FasL, thus inhibiting HO-induced apoptosis of PGCs. PAP significantly reduces p-JNK expression and increases the p-FoxO1/FoxO1 expression ratio, thereby decreasing caspase-3 expression and cell apoptosis in HO-induced PGCs. PAP promotes the combination of FoxO1 with the 14-3-3 protein, increases FoxO1 translocation to the cytoplasm, and decreases FoxO1 acetylation. Therefore, PAP regulates FoxO1 expression through the JNK/FoxO1 signaling pathway and effects the translocation of FoxO1 to the cytoplasm by the FoxO1 interaction with 14-3-3, enabling reversal of the HO-induced apoptosis of PGCs. Acetylation of FoxO1 is also involved in the antiapoptotic effect of PAP.
10.1016/j.theriogenology.2022.02.004
Antioxidative effect of extract on dextran sulfate sodium-induced ulcerative colitis through activation of the Nrf2 signal.
Pharmaceutical biology
CONTEXT: L. (Blattariae) is used as a treatment for ulcerative colitis (UC) in Chinese traditional medicine. OBJECTIVE:To evaluate the antioxidative activity of whole body ethanol extract (PAE) on UC mice and whether glycine and proline could be used for quality control and identification of active PAE components. MATERIALS AND METHODS:NCM460 cells were pre-incubated in PAE, AA-L, AA-M, and AA-H (low, high and medium doses of proline and glycine), then treated with recombinant human TNF-α. The glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen (ROS) levels were determined. UC mice were fed with water containing 2.5% dextran sulfate sodium (w/v) after pre-treatment with different doses of PAE once a day for 7 days. ELISA was used to detect the concentrations of inflammation-related factors. Colon tissues of mice were used to detect the activity of myeloperoxidase (MPO), GSH, MDA, and SOD. Histological changes were observed using H&E staining. The expression of target proteins was determined by western blotting. RESULTS:, PAE treatment reduced the DAI score more than in the model group, restoring the weight and colonic length. It also reduced the severity of colitis, and inflammatory and oxidative stress intensity. Additionally, western blotting showed that the Nrf2 pathway was activated by PAE. PAE significantly alleviated TNF-α-induced cell damage and oxidative stress, which is relevant to the activation of the Nrf2 pathway. CONCLUSIONS:PAE may relieve oxidative stress through the Nrf2 signaling pathway, and proline and glycine may be used as active components of its antioxidative stress activity.
10.1080/13880209.2023.2220351
Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation.
International journal of biological macromolecules
Along with the increasing attempts to explore the wound healing effective substances of Periplaneta americana (L.) (PA), a medicinal insect in traditional Chinese medicine, researchers' attention turned to the endogenetic macromolecules, such as polysaccharides and peptides. Herein, we innovatively isolated two glycoproteins from PA, named PAGP-1 and PAGP-2, which were obtained by Cellulose DE-52 chromatography and purified by Sephadex G-100 gel in succession. The structural characterization of the two PAGPs were performed, including molecular weight, amino acid and monosaccharide composition, morphology analysis, FT-IR and H NMR analysis, CD spectroscopy, and glycosides linkage. As a result, two PAGPs belonged to O-glycopeptide bonds linked glycoproteins. The content of carbohydrate and protein of PAGP-1 was approximately 25.23% and 65.92% respectively, which of PAGP-2 was approximately 25.71% and 71.23%. Based on the remarkable anti-inflammatory effects of PAGPs on LPS-induced RAW264.7 cells, the topical administration of PAGP-1 and PAGP-2 could significantly accelerate full-thickness wound healing in diabetic mice, involving to alleviate the inflammation, increase the ratio of type I and type III collagen fibers, and promote the polarization of macrophages M1 to M2. In short, this study provides clear evidence that the glycoproteins would be the potential wound healing bioactive substances in PA.
10.1016/j.ijbiomac.2022.04.193
Periplaneta americana extract promotes osteoblast differentiation of human alveolar bone marrow mesenchymal stem cells.
Oral diseases
OBJECTIVES:This study aims to investigate the effects of Traditional Chinese medicine, Periplaneta americana extract (PAE), on osteoblast differentiation of human alveolar bone marrow-derived mesenchymal stem cells (hABMMSCs). MATERIALS AND METHODS:Human alveolar bone marrow-derived mesenchymal stem cells were treated with different concentrations of PAE. Cell Counting Kit-8 (CCK-8) assay and transwell migration assay were conducted to evaluate cell proliferation and migration, respectively. Alkaline phosphatase (ALP) staining, ALP activity assay, and Alizarin red S staining were performed to detect osteogenesis in hABMMSCs. In addition, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) assay were performed to evaluate expression levels of osteogenic markers. Finally, RNA sequencing analysis and WB were carried out to elucidate the underlying mechanism. RESULTS:A total of 0.1 mg/ml PAE promoted cell proliferation and migration. PAE also increased ALP activity and mineralized nodule formation of hABMMSCs. In addition, PAE upregulated the expression of osteogenesis-related genes (RUNX2, COL1A1, and BGLAP). RNA-sequencing analysis revealed that PAE activated the focal adhesion signaling pathway. Treatment with Defactinib, an inhibitor of FAK, attenuated the effects induced by PAE. CONCLUSIONS:PAE could enhance osteoblast differentiation of hABMMSCs through focal adhesion signaling pathway, suggesting a therapeutic potential for the alveolar bone defect.
10.1111/odi.14470
Extracts Accelerate Liver Regeneration a Complex Network of Pathways.
Zou Yingying,Zhang Meiyan,Zeng Di,Ruan Yonghua,Shen Lijuan,Mu Zhihao,Zou Jiangmeng,Xie Chenjian,Yang Zhihong,Qian Zhongyi,Xu Ruobing,Li Shude,Kang Qiang,Zou Hao,Zhao Songling,Liu Lixin,Wang Kun,Wang Xie,Zhang Xiaowen
Frontiers in pharmacology
Successful recovery from hepatectomy is partially contingent upon the rate of residual liver regeneration. The traditional Chinese medicines known as extracts (PAEs) positively influence wound healing by promoting tissue repair. However, the effect of PAEs on liver regeneration is unknown. We used a mouse liver regeneration model after 70% partial hepatectomy (PH) and a hepatocyte culture to determine whether PAEs can promote liver regeneration as effectively as skin regeneration and establish their modes of action. L02 cells were divided into serum-starved control (NC) and three PAEs (serum starvation + 0.1 mg/ml, 0.5 mg/ml, or 1 mg/ml PAEs) groups. L02 cell proliferation was assessed at 24 h, 48 h, and 72 h by CCK-8 assay. Forty male C57 mice were randomly divided into control (NC), normal saline (NS), PAEs400 (400 mg/kg/d), and PAEs800 (800 mg/kg/d) groups (n = 10 per group). The NS and both PAEs groups were administered normal saline and PAEs, respectively, by gavage for 10 days. Two hours after the tenth gavage, the NS and both PAEs groups were subjected to 70% PH and the residual liver was harvested after 48 h. The hepatic regeneration rate was evaluated and hepatocyte proliferation was estimated by immunohistochemical (IHC) staining for Ki-67. Twelve DEG libraries (three samples per group) were prepared and sequencing was performed in an Illumina HiSeq 2000 (Mus_musculus) at the Beijing Genomics Institute. The genes expressed in the liver tissues and their expression profiles were analyzed by bioinformatics. KEGG was used to annotate, enrich, and analyze the pathways. PAEs promoted hepatocyte proliferation and and accelerated mouse liver regeneration after 70% PH. The screening criteria were fold change (FC) ≥ 2 and q-value < 0.001. We identified 1,092 known DEGs in PAEs400 and PAEs800. Of these, 153 were categorized in cellular processes. The KEGG analysis revealed that the aforementioned DEGs participated in several signaling pathways closely associated with cell proliferation including PI3K-Akt, MAPK, Apelin, Wnt, FoxO, mTOR, Ras, VEGF, ErbB, Hippo, and AMPK. It was concluded that PAEs can effectively improve liver regeneration the synergistic activation of different signaling pathways.
10.3389/fphar.2020.01174
Chitosan electrospun nanofibers derived from Periplaneta americana residue for promoting infected wound healing.
International journal of biological macromolecules
Periplaneta americana has been used medicinally for years to treat a wide variety of skin lesions or ulcers. However, a sizable portion of the drug residues that are retained after extraction are routinely thrown away, thus posing a hazard to the environment and depleting resources. In this study, low molecular weight Periplaneta americana chitosan (LPCS) and high molecular weight Periplaneta americana chitosan (HPCS) were extracted from Periplaneta americana residue (PAR) based on the conventional acid-base method and two deacetylation methods. Moreover, the physicochemical properties and structural differences between the above two chitosan and commercial chitosan (CS) were compared using different methods. Next, two nanofibers comprising different ratios of Periplaneta americana chitosan (LPCS or HPCS), polyvinyl alcohol (PVA), and polyethylene oxide (PEO) were prepared and optimized. The above nanofibers exhibited excellent mechanical properties, antibacterial properties, and biocompatibility while facilitating wound healing in an infected rat whole-layer wound model by promoting wound closure, epithelialization, collagen deposition, and inflammation reduction. In brief, this study produced an effective and affordable wound dressing and offered a suggestion for the comprehensive utilization of Periplaneta americana residue.
10.1016/j.ijbiomac.2022.12.272
Natural exosome-like nanoparticles derived from ancient medicinal insect Periplaneta americana L. as a novel diabetic wound healing accelerator.
Journal of nanobiotechnology
Along with the recognized therapeutic outcomes of regenerative medicine, extracellular vesicles and their exosome subsets have become an alternative option for wound healing. Periplaneta americana L. (PA), an ancient and traditional medicinal insect, has been around for 300 million years, and displays magic formidable vitality and environmental adaptive ability. The linkage between intrinsic amputation regeneration feature and the acknowledged wound healing medicinal benefit of PA has never been revealed. Herein, inspired by the ability of exosomes to participate in the interkingdom communication, we explored whether this effect was ascribed to PA derived exosome-like nanoparticles (PA-ELNs). PA-ELNs were extracted by differential velocity centrifugation approach and characterized by DLS, NTA and TEM. Their cargoes were analyzed by LC-MS/MS proteomics and small RNA-seq analysis. The wound healing activity was verified in vivo and in vitro. PA-ELNs with a concentration of 2.33x10±6.35x10 particles/mL exhibited a lipid bilayer-bound membrane structure with an average size of 104.7 nm. Furthermore, the miRNA cargoes in PA-ELNs participate in some wound healing related signal pathways such as TGF-beta, mTOR, and autophagy. As expected, the in vitro tests indicated that PA-ELNs were apt to be internalized in HUVECs, L929 and RAW 264.7 cells and contributed to cell proliferation and migration. Most importantly, we demonstrated that the topical administration of PA-ELNs could remarkably accelerate wound healing in a diabetic mouse model, and was involved in anti-inflammatory, re-epithelialization and autophagy regulation. This study provides clear evidence for the first time that PA-ELNs, as diabetic wound healing accelerators, are the "bioactive code" of this ancient medicinal insect.
10.1186/s12951-023-01923-1
Characterization and diabetic wound healing benefits of protein-polysaccharide complexes isolated from an animal ethno-medicine Periplaneta americana L.
Liao Qian,Pang Lan,Li Jing-Jing,Zhang Chen,Li Jia-Xing,Zhang Xing,Mao Ting,Wu Ding-Tao,Ma Xiu-Ying,Geng Fu-Neng,Zhang Jin-Ming
International journal of biological macromolecules
Periplaneta americana L. (PA), a type of animal medicine, has been widely used for wound healing in clinical settings. In order to further investigate the bioactive wound healing substances in PA, crude PA protein-polysaccharide complexes were further purified by cellulose DE-52 and Sephadex G100 chromatography in succession. Among these isolated fractions, two fractions eluted by 0.3 M and 0.5 M NaCl with the higher yield, respectively named PaPPc2 and PaPPc3 respectively, were chosen for the wound healing experiments. Mediated by HPGPC, amino acid and monosaccharide composition analysis, circular dichroism spectrum, glycosylation type, FT-IR, and H NMR analysis, the characterization of PaPPc2 and PaPPc3 was implemented. And then, the benefits of PaPPcs to promote cell proliferation, migration, and tube formation of HUVECs were determined in vitro, indicated these fractions would facilitate angiogenesis. Finally, as proof of concept, PaPPc2 and PaPPc3 were employed to accelerate the acute wounds of diabetic mice, involving in increase blood vessels and the amounts of angiogenesis-related cytokines (α-SMA, VEGF, and CD31). In short, this study provides an experimental basis to demonstrate the protein-polysaccharide complexes of Periplaneta americana L. as its wound healing bioactive substances.
10.1016/j.ijbiomac.2021.12.018
The ethanol extract of Periplaneta Americana L. improves ulcerative colitis induced by a combination of chronic stress and TNBS in rats.
Acta cirurgica brasileira
PURPOSE:To investigate the effects of Periplaneta americana L. on ulcerative colitis (UC) induced by a combination of chronic stress (CS) and 2,4,6-trinitrobenzene sulfonic acid enema (TNBS) in rats. METHODS:The experiment UC model with CS was established in rats by a combination of chronic restraint stress, excess failure, improper, and TNBS. The body weight, disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS) and pro-inflammatory mediators were measured. The content of corticotropin-releasing hormone (CRH) in hypothalamus or adrenocorticotropic hormone (ACTH) and corticosteroids (CORT) in plasma were evaluated by enzyme-linked immunosorbent assay. The proportion of T lymphocyte subsets was detected by flow cytometry, and gut microbiota was detected by 16S rDNA amplicon sequencing. RESULTS:Weight loss, DAI, CMDI, HS and proinflammatory mediators were reversed in rats by P. americana L. treatment after UC with CS. Increased epidermal growth factor (EGF) was observed in P. americana L. groups. In addition, P. americana L. could reduce the content of CRH and ACTH and regulate the ratio of CD3+, CD3+CD8+ and CD3+CD4+CD25+/CD4+ in spleen. Comparably, P. americana L. changes composition of gut microbiota. CONCLUSIONS:The ethanol extract of Periplaneta Americana L. improves UC induced by a combination of CS and TNBS in rats.
10.1590/acb370505
The inhibitory effect of Periplaneta americana L. on hepatocellular carcinoma: Explore the anti-hepatocellular carcinoma active site and its mechanism of action.
Ma Hongyan,Li Xue,Che Jing,Fan Hong,Liu Qian,Xia Houlin
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:The American cockroach (Periplaneta americana L.) belongs to the family Blattidae, order Blattodea, and class Insecta. Its medicinal history in China spans thousands of years. In recent years, the anti-tumour activity of American cockroach has gradually attracted the attention of researchers and has a good application prospect in the treatment of tumours. Periplaneta americana has been found to contain proteins, peptides, amino acids and nucleosides. Pharmacological studies have shown that P. americana has anti-tumour, tissue repair, immunoregulatory and other activities. In this study, we investigated the chemical composition and mechanism of action of its active site against hepatocellular carcinoma. MATERIALS AND METHODS:We adopted ultra-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS), measuring the accurate relative molecular mass, fragment ion peak, chromatographic retention time and reference substance information of the compound obtained by HRMS, to identify the chemical components of the anti-hepatocellular carcinoma (HCC) active site of P. americana based on data from relevant literature. We used western blotting (WB) to detect the expression levels of phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt) and Akt in the PI3K/Akt pathway and further study the molecular mechanism of the active site of P. americana against HCC. RESULTS:UPLC-Q-Orbitrap HRMS identified 35 compounds from the active site of P. americana. Of these, 10 were amino acids, 1 was an alkaloid, 6 were nucleosides and their bases, 4 were dipeptides and cyclic dipeptides, 8 were organic acids, 2 were isoflavones and 4 were other compounds; 8 of these compounds were confirmed by comparison with the reference substance. The WB results showed that the relative expression levels of PI3K and p-Akt protein in the active site of P. americana in the medium-dose (concentration, 0.15624 mg⋅mL) and high-dose (concentration, 0.31250 mg⋅mL1) experimental groups were significantly reduced compared with the blank control group (P < 0.05 or P < 0.01), whereas the expression level of Akt protein did not significantly change amongst the groups (P > 0.05). CONCLUSION:This study found that the anti-HCC active site of P. americana is composed of multiple components that can reduce the relative expression of PI3K and p-Akt protein. It exerts its anti-HCC effect by regulating the PI3K/Akt pathway.
10.1016/j.jep.2021.114884
Discovery of indole analogues from extract and their activities on cell proliferation and recovery of ulcerative colitis in mice.
Frontiers in pharmacology
As an important medicinal insect, (PA) has been applied for the treatment of wounds, burns, and ulcers with fewer side effects and a reduced recurrence rate, which provides great potential for developing new drugs based on its active constituents. The main chromatographic peaks determined by high performance liquid chromatography (HPLC) in the PA concentrated ethanol-extract liquid (PACEL) were separated, purified, and identified by semi-preparative LC, mass spectrum, and H NMR spectroscopic analysis. The biological activities of the identified compounds were investigated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) method based on human skin fibroblasts (HSF) and experiments based on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model. Furthermore, RT-qPCR of six genes related to inflammation or intestinal epithelial cell proliferation was employed to investigate the molecular mechanism of the indole analogues recovering UC in mice. Five indole analogues were purified and identified from PACEL, including tryptophan (Trp), tryptamine (pa01), 1,2,3,4-tetrahydrogen-β-carboline-3-carboxylic acid (pa02), (1S, 3S)-1-methyl-1,2,3,4-tetrahydrogen-β-carboline-3-carboxylic acid (pa03), and (1R, 3S)-1-methyl-1,2,3,4-tetrahydrogen-β-carboline-3-carboxylic acid (pa04), among which the pa02 and pa04 were reported in PA for the first time. and experiments showed that PACEL, Trp, and pa02 had promoting HSF proliferation activity and intragastric administration of them could alleviate symptoms of weight loss and colon length shortening in the UC mice. Although recovery activity of the compound pa01 on the colon length was not as obvious as other compounds, it showed anti-inflammatory activity in histological analysis. In addition, The RT-qPCR results indicated that the three indole analogues could alleviate DSS-induced intestinal inflammation in mice by inhibiting pro-inflammatory cytokines (, ) and down-regulating expression. This study reported the isolation, purification, structure identification, and biological activity of the active indole analogues in PACEL. It was found for the first time that the PA extract contained many indole analogues and Trp, which exhibited good proliferation activity on HSF fibroblasts as well as anti-UC activity in mice. These indole analogues probably are important components related to the pharmacological activity in PA.
10.3389/fphar.2023.1282545
Extracts of Periplaneta americana alleviate hepatic fibrosis by affecting hepatic TGF-β and NF-κB expression in rats with pig serum-induced liver fibrosis.
Folia histochemica et cytobiologica
INTRODUCTION:Liver fibrosis is caused by continuous wound healing responses to various harmful stimuli, including viral infection, drugs, alcohol, and autoimmune liver disease. The purpose of this study was to examine the effects of extracts of Periplaneta americana (EPA) in rats with pig serum-induced liver fibrosis to preliminarily assess the antifibrotic effect of EPA. MATERIAL AND METHODS:Seventy rats were randomly divided into 7 groups (10 rats in each group): HC, the healthy control group; FC, the fibrotic control group; TL, low-dose EPA treatment group group; TM, medium-dose EPA group; TH, high-dose EPA treatment group; TC1, Panax notoginseng/Salvia mitiorrhiza treatment control group 1; TC2, colchicine treatment control group 2. TC1 and TC2 were used as the positive control to demonstrate the difference between EPA and the effects of other compounds. The liver fibrosis model was induced by intraperitoneal injection of 0.5 mL pig serum twice a week for 13 weeks in all groups except for the HC group. The hepatic fibrosis model was established at the 7th week, and followingly, the corresponding compounds were administered once a day in all groups for 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity was determined in rat blood serum. We also measured liver fibrosis-related serum markers, including hyaluronic acid (HA), mucin layer (LN), type III pre-collagen (PC-III) and type IV collagen (IV-C). Hematoxylin and eosin (H&E) and Masson stainings were used to assess liver morphology and determine the stage of fibrosis. Immunohistochemistry was used to detect the protein expression of NF-κB, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rat liver tissue. RESULTS:Compared with that of the HC group, the liver tissue of the FC group presented obvious liver damage and collagen deposition. The serum levels of ALT, AST, HA, LN, PC-III and IV-C and the expression of NF-κB, α-SMA, TGF-β1 and TIMP-1 in the FC group were significantly higher than those in the HC group, the EPA treatment groups, the TC1 group and the TC2 group (P < 0.01). The levels of serum ALT, AST, HA, LN, PC-III and IV-C and the expression of α-SMA, NF-κB, TGF-β1 and TIMP-1 in the TL, TC1 and TC2 groups were significantly higher than those TM and TH groups (P < 0.05). EPA treatment significantly improved liver function, decreased collagen deposition and reversed the pathological changes related to liver fibrosis. CONCLUSIONS:We found that EPA could reduce liver inflammation, suppress liver cell degeneration and necrosis, and reduce the formation of liver fibrous tissue. Its mechanism might be associated with inhibiting the expression of TGF-β1, TIMP-1, NF-κB and α-SMA to block signal transduction pathways in the hepatic fibrosis process. Therefore, EPA, as a traditional Chinese medicine, might be potentially used to prevent and treat hepatic fibrosis in the future. However, further more experiments are necessary to verify its effectiveness and possible signaling pathways.
10.5603/FHC.a2022.0011
Effects of extracts on the growth and proliferation of cutaneous interstitial cells in cutaneous-wound healing.
Frontiers in pharmacology
Cutaneous-wound healing requires a coordinated reaction of multiple cells, including interstitial cells. Impaired recovery of cutaneous wounds can lead to various adverse health outcomes. Kangfuxin (KFX), an extract obtained from is beneficial in cutaneous-wound healing. In this study, we isolated dermal cells from suckling mice and established a mouse model of cutaneous injury to evaluate the therapeutic effects of KFX. Cell biology experiments indicated that treatment with KFX improved cell proliferation and migration and also repaired cutaneous wounds in the animal model. Activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway was the core molecular mechanism of KFX. Our study provides a theoretical and practical basis for the clinical application of KFX in cutaneous-wound healing.
10.3389/fphar.2022.920855
Antipyretic, anti-inflammatory and analgesic activities of Periplaneta americana extract and underlying mechanisms.
Nguyen Tienthanh,Chen Xin,Chai Jinwei,Li Rui,Han Xiaoyan,Chen Xiaoxin,Liu Shuwen,Chen Ming,Xu Xueqing
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Periplaneta americana is a common traditional Chinese medicinal material which has been used to treat arthritis, fever, aches, pains, and inflammation of the extremities for several hundred years. However, little scientific data exists in literature to support its use. The purpose of this study was to evaluate the antipyretic, anti-inflammatory and analgesic activities of Periplaneta americana extract (PAE) and explore its underlying mechanism. The antipyretic, anti-inflammatory and analgesic activities were evaluated by LPS-induced fever, carrageenan-induced paw edema, abdominal writhing, hot plate and formalin tests, respectively. The mechanism of action was explored by antioxidant activity analysis, inflammatory cytokines expression and febrile mediator measurement, and pathway activation analysis. The results from UHPLC-HRMS indicated that the extract was found to contain dopamine, coumarin, dipeptide, vitamin, organic acid, amino acid and its metabolites, and other organic compounds. PAE showed in a dose-dependent manner antioxidant activity and reduced the protein production and mRNA expression of NO, IL-1β, IL-6, and TNF-α in RAW 264.7 cells in vitro. Moreover, PAE significantly and dose-dependently inhibited the writhing responses and licking time in formalin tests, increased response latency in the hot plate test, reduced carrageenan-induced paw edema and inflammation in mice, decreased LPS-induced rT increase in rats. Furthermore, PAE treatment markedly inhibited the increase in the levels of NO, IL-6, IL-1β, TNF-α, PGE and cAMP in plasma of fevered rat, greatly suppressed the activation of inflammatory response pathway and the change of MDA and GSH concentration, MPO and SOD activity as well as FRAP capacity in paw induced by carrageenan injection. In conclusion, the findings suggested that PAE produced potential antinociceptive, anti-inflammatory and antipyretic effects by reducing production of endogenous inflammatory mediators and blocking the MAPK/NF-κB signaling pathway which support the claim for its traditional use in the treatment of various diseases.
10.1016/j.biopha.2019.109753
Oligosaccharides Exert Anti-Inflammatory Activity through Immunoregulation and Modulation of Gut Microbiota in Acute Colitis Mice Model.
Lu Kaimin,Zhou Jing,Deng Jie,Li Yangjun,Wu Chuanfang,Bao Jinku
Molecules (Basel, Switzerland)
The incidence and prevalence of inflammatory bowel disorders (IBD) are increasing around the world due to bacterial infection, abnormal immune response, etc. The conventional medicines for IBD treatment possess serious side effects. (), a traditional Chinese medicine, has been used to treat arthritis, fever, aches, inflammation, and other diseases. This study aimed to evaluate the anti-inflammatory effects of oligosaccharides from (OPA) and its possible mechanisms in vivo. OPA were purified and biochemical characterization was analyzed by HPGPC, HPLC, FT-IR, and GC-MS. Acute colitis mice model was established, the acute toxicity and anti-inflammatory activity were tested in vivo. The results showed OPA with molecular mass of 1.0 kDa were composed of 83% glucose, 6% galactose, 11% xylose, and the backbone was (1→4)-Glcp. OPA had potent antioxidant activities in vitro and significantly alleviated the clinical symptoms of colitis, relieved colon damage without toxic side effects in vivo. OPA exhibited anti-inflammatory activity by regulating Th1/Th2, reducing oxidative stress, preserving intestinal barrier integrity, and inhibiting TLR4/MAPK/NF-κB pathway. Moreover, OPA protected gut by increasing microbial diversity and beneficial bacteria, and reducing pathogenic bacteria in feces. OPA might be the candidate of complementary and alternative medicines of IBD with low-cost and high safety.
10.3390/molecules26061718
Periplaneta Americana L. as a novel therapeutics accelerates wound repair and regeneration.
Li Long-Jian,Xu Xue-Han,Yuan Tie-Jun,Hou Jian,Yu Chui-Liang,Peng Li-Hua
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Kangfuxin (KFX) is the ethanol extract of Periplaneta Americana L., which has been widely used in Traditional Chinese Medicine for the treatment of injury in clinic with a long history. However, the biological influence of KFX in the different wound stages was not investigated comprehensively yet. This study aims to investigate the influence of KFX in the various wound healing activities with cellular and animal models, including the influence of KFX in 1) proliferation and cells cycle of kerationcytes and fibroblasts; 2) migration and chemotaxis of these skin cells; 3) secretion of EGF and VEGF; 4) the healing rate; 5) synthesis and deposition of different types of collagen; 6) as well as the pro-angiogenesis effect. KFX was shown to/for 1) promote the kerationcytes proliferation and regulate the cells cycle of skin fibroblasts significantly; 2) obviously stimulate the migration of kerationcytes and chemotaxis of fibroblasts; 3) the trend to promote EGF and VEGF secretion both in vitro & in vivo; 4) accelerate the wound closure, collagen synthesis and angiogenesis. KFX was demonstrated to accelerate wound healing and improve the healing quality by multiple regulation. Results of this study provide the comprehensive evidence for the application of KFX as a novel therapeutics for wound treatment.
10.1016/j.biopha.2019.108858
Extract Pretreatment Alleviates Oxidative Stress and Inflammation and Increases the Abundance of Gut in Diquat-Induced Mice.
Antioxidants (Basel, Switzerland)
Studies have shown that extract (PAE) has good therapeutic effects in inflammatory disorders such as ulcerative colitis, alcoholic hepatitis, and gastric ulcers. However, whether or not PAE has good pre-protective effects has not been widely and deeply studied. In this study, we investigated the effects of PAE pretreatment for 7 days on oxidative stress and inflammation triggered by oxidative stress by using diquat-induced C57BL/6 mice as an oxidative stress model. The results showed that PAE pretreatment could significantly reduce oxidative stress in the intestine and liver by reducing the production of MDA, and improved antioxidant systems (SOD, CAT, GSH, and T-AOC). By primarily activating the anti-inflammatory cytokine (IL-10) mediated JAK1/STAT3 signaling pathway, PAE also effectively reduced oxidative stress-induced liver inflammation while also reducing liver damage, as evidenced by the reductions in serum AST and ALT. PAE pretreatment also had a significant effect on maintaining the intestinal barrier function, which was manifested by inhibiting a decrease in the expression of tight junction proteins (ZO-1 and occludin), and reducing the increased intestinal permeability (serum DAO and D-Lac) caused by diquat. The 16S rRNA sequencing analysis revealed that diquat decreased the gut microbiota diversity index and increased the abundance of pathogenic bacteria (e.g., , and ), while PAE pretreatment responded to diquat-induced damage by greatly increasing the abundance of . These findings elucidate potential pre-protective mechanisms of PAE in alleviating oxidative stress and inflammation, while providing a direction for the treatment of metabolic diseases by utilizing PAE to enhance the abundance of gut .
10.3390/antiox11091806
Antioxidant, antibacterial, and anti-inflammatory Periplaneta americana remnant chitosan/polysaccharide composite film: In vivo wound healing application evaluation.
International journal of biological macromolecules
Periplaneta americana (P. americana), which is widely used for wound healing in China, produces a large amount of solid waste (P. americana remnant) after pharmaceutical production extraction. P. americana remnant chitosan (PAC) has a low molecular weight, low crystallinity, and easily modifiable structural properties. In this study, PAC and P. americana remnant polysaccharide (PAP) were used as raw materials to prepare a composite film (PAPCF). The good biocompatibility of the composite film was verified by cell proliferation assays and protein adsorption assays. The bioactivity of the composite film was assessed by antibacterial and in vivo/vitro antioxidant assays to evaluate its potential as a wound dressing. The wound healing experiment revealed that PAPCF improved wound closure and collagen deposition, decreased reactive oxygen species levels, and attenuated the inflammatory response, enabling rapid wound healing from the inflammatory phase to the proliferative phase in mice. Additionally, PAPCF was administered only once, reducing the chance of infection from multiple deliveries. In summary, this paper presents an easy-to-administer, cost-effective, and effective dressing candidate for wound treatment based on the environmental concept of resource reuse.
10.1016/j.ijbiomac.2023.124068
Periplaneta americana extract ameliorates dextran sulfate sodium-induced ulcerative colitis via immunoregulatory and PI3K/AKT/NF-κB signaling pathways.
Inflammopharmacology
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with a low cure rate. Periplaneta americana is a traditional American Cockroach and reportedly has potential therapeutic roles for UC treatment; however, its mechanisms remain unclear. To address this, we investigated the therapeutic effects and underlying molecular mechanisms of Ento-A, a Periplaneta americana extract, in a dextran sulfate sodium (DSS)-induced chronic and recurrent UC mouse model. Ento-A treatment decreased pro-inflammatory cytokine secretion, disease activity index (DAI), colon mucosa damage index (CMDI), histopathological scores (HS), and increased colon length. Additionally, Ento-A effectively increased interleukin-4 (IL-4), and forkhead transcription factor protein 3 (Foxp3) expression levels, while it abated interferon-γ (IFN-γ) and IL-17 levels in spleen lymphocytes. Conversely, in mesenteric lymph nodes, IL-4 and Foxp3 expression were decreased, while IFN-γ and IL-17 expression was increased. Furthermore, Ento-A blocked p-PI3K, p-AKT,*and p-NF-κB activation. In conclusion, Ento-A improved UC symptoms and exerted therapeutic effects by regulating immune responses and inhibiting PI3K/AKT/NF-κB signaling.
10.1007/s10787-022-00955-7
Periplaneta Americana (L.) extract activates the ERK/CREB/BDNF pathway to promote post-stroke neuroregeneration and recovery of neurological functions in rats.
Journal of ethnopharmacology
ETHNOPHARMACOLOGICAL RELEVANCE:Periplaneta americana (L.) (PA) has been used in traditional Chinese medicine for thousands of years for the effect of invigorating blood circulation and removing blood stasis. Modern pharmacological research shown that PA extract exhibits promising effects in promoting wound healing and regeneration, as well as in brain diseases such as Parkinson's disease (PD). However, whether it is effective for neuroregeneration and neurological function recovery after stroke still unknown. AIM OF THE STUDY:This study aims to investigate the potential effect of PA extract to promote brain remodeling through the activation of endogenous neurogenesis and angiogenesis, in addition, preliminary exploration of its regulatory mechanism. METHODS:Firstly, BrdU proliferation assay and immunofluorescence (IF) staining were used to evaluate the effect of PA extract on the neurogenesis and angiogenesis in vitro and in vivo. Subsequently, the effects of PA extract on brain injury in stroke rats were assessed by TTC and HE. While mNSS score, adhesive removal test, rota-rod test, and morris water maze test were used to assess the impact of PA extract on neurological function in post-stroke rats. Finally, the molecular mechanisms of PA extract regulation were explored by RNA-Seq and western blotting. RESULTS:The number of BrdU cells in C17.2 cells, NSCs and BMECs dramatically increased, as well as the expression of astrocyte marker protein GFAP and neuronal marker protein Tuj-1 in C17.2 and NSCs. Moreover, PA extract also increased the number of BrdUDCX, BrdUGFAP, BrdUCD31 cells in the SGZ area of transient middle cerebral artery occlusion model (tMCAO) rats. TTC and HE staining revealed that PA extract significantly reduced the infarction volume and ameliorated the pathological damage. Behavioral tests demonstrated that treatment with PA extract reduced the mNSS score and the time required to remove adhesive tape, while increasing the time spent on the rotarod. Additionally, in the morris water maze test, the frequency of crossing platform and the time spent in the platform quadrant increased. Finally, RNA-Seq and Western blot revealed that PA extract increased the expression of p-ERK, p-CREB and BDNF. Importantly, PA extract mediated proliferation and differentiation of C17.2 and NSCs reversed by the ERK inhibitor SCH772984 and the BDNF inhibitor ANA-12, respectively. CONCLUSION:Our study demonstrated that PA extract promoted neurogenesis and angiogenesis by activating the CREB/ERK signaling pathway and upregulating BDNF expression, thereby recovering neurological dysfunction in post-stroke.
10.1016/j.jep.2023.117400
Periplaneta Americana Extract Ameliorates LPS-induced Acute Lung Injury Via Reducing Inflammation and Oxidative Stress.
Current medical science
OBJECTIVE:Acute lung injury (ALI) is an acute clinical syndrome characterized by uncontrolled inflammation response, which causes high mortality and poor prognosis. The present study determined the protective effect and underlying mechanism of Periplaneta americana extract (PAE) against lipopolysaccharide (LPS)-induced ALI. METHODS:The viability of MH-S cells was measured by MTT. ALI was induced in BALB/c mice by intranasal administration of LPS (5 mg/kg), and the pathological changes, oxidative stress, myeloperoxidase activity, lactate dehydrogenase activity, inflammatory cytokine expression, edema formation, and signal pathway activation in lung tissues and bronchoalveolar lavage fluid (BALF) were examined by H&E staining, MDA, SOD and CAT assays, MPO assay, ELISA, wet/dry analysis, immunofluorescence staining and Western blotting, respectively. RESULTS:The results revealed that PAE obviously inhibited the release of proinflammatory TNF-α, IL-6 and IL-1β by suppressing the activation of MAPK/Akt/NF-κB signaling pathways in LPS-treated MH-S cells. Furthermore, PAE suppressed the neutrophil infiltration, permeability increase, pathological changes, cellular damage and death, pro-inflammatory cytokines expression, and oxidative stress upregulation, which was associated with its blockage of the MAPK/Akt/NF-κB pathway in lung tissues of ALI mice. CONCLUSION:PAE may serve as a potential agent for ALI treatment due to its anti-inflammatory and anti-oxidative properties, which correlate to the blockage of the MAPK/NF-κB and AKT signaling pathways.
10.1007/s11596-023-2723-8