Thermodynamics driving phytochemical self-assembly morphological change and efficacy enhancement originated from single and co-decoction of traditional chinese medicine.
Journal of nanobiotechnology
Through the self-assembled strategy to improve the clinical efficacy of the existing drugs is the focus of current research. Herbal formula granule is a kind of modern dosage form of traditional Chinese medicine (TCM) which has sprung up in recent decades. However, whether it is equivalent to the TCM decoction that has been used for thousands of years has always been a controversial issue. In this paper, taking the herb pair of Coptidis Rhizoma-Scutellariae Radix and its main component berberine-baicalin as examples, the differences and mechanisms of self-assemblies originated from the co-decoction and physical mixture were studied, respectively. Moreover, the relationship between the morphology and antibacterial effects of self-assemblies was illuminated via multi-technology. Our study revealed that the physical mixture's morphology of both the herb pair and the phytochemicals was nanofibers (NFs), while their co-decoction's morphology was nanospheres (NPs). We also found that the antibacterial activity was enhanced with the change of self-assemblies' morphology after the driving by thermal energy. This might be attributed to that NPs could influence amino acid biosynthesis and metabolism in bacteria. Current study provides a basis that co-decoction maybe beneficial to enhance activity and reasonable use of herbal formula granule in clinic.
10.1186/s12951-022-01734-w
A hydrogen-bonded antibacterial curdlan-tannic acid hydrogel with an antioxidant and hemostatic function for wound healing.
Zhou Zongbao,Xiao Jiangwei,Guan Shuwen,Geng Zhijie,Zhao Ruifang,Gao Botao
Carbohydrate polymers
Manufacturing facile and low-cost wound dressings that simultaneously meet the needs of the entire repair process remains the major challenge of effective wound healing. Herein, a series of curdlan-tannic acid hybrid hydrogels were successfully fabricated through the annealing technique. Notedly, when the mixing weigh ratio was 1:1, the hydrogel exhibited excellent physicochemical properties, including swellability, degradability, water retention, porosity, and rheology. Additionally, the hydrogel did not display significant cytotoxicity to fibroblasts and the hemolysis rate at 12 h was 3%. Interestingly, the hybrid hydrogel showed multifunctional properties, including remarkable antioxidant, antibacterial, and rapid hemostasis effects reduce blood loss by 0.35 g, that were achieved through the temperature-dependent release of tannic acid. Moreover, a full-thickness skin defect animal model was used to verify that the multifunctional hydrogel could accelerate wound healing in vivo. These results suggest that this hybrid hydrogel is a promising candidate for the clinical treatment of full-thickness wounds.
10.1016/j.carbpol.2022.119235
Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation.
Zheng Jun,Fan Rong,Wu Huiqiong,Yao Honghui,Yan Yujie,Liu Jiamiao,Ran Lu,Sun Zhifang,Yi Lunzhao,Dang Li,Gan Pingping,Zheng Piao,Yang Tilong,Zhang Yi,Tang Tao,Wang Yang
Nature communications
Self-assembling natural drug hydrogels formed without structural modification and able to act as carriers are of interest for biomedical applications. A lack of knowledge about natural drug gels limits there current application. Here, we report on rhein, a herbal natural product, which is directly self-assembled into hydrogels through noncovalent interactions. This hydrogel shows excellent stability, sustained release and reversible stimuli-responses. The hydrogel consists of a three-dimensional nanofiber network that prevents premature degradation. Moreover, it easily enters cells and binds to toll-like receptor 4. This enables rhein hydrogels to significantly dephosphorylate IκBα, inhibiting the nuclear translocation of p65 at the NFκB signalling pathway in lipopolysaccharide-induced BV2 microglia. Subsequently, rhein hydrogels alleviate neuroinflammation with a long-lasting effect and little cytotoxicity compared to the equivalent free-drug in vitro. This study highlights a direct self-assembly hydrogel from natural small molecule as a promising neuroinflammatory therapy.
10.1038/s41467-019-09601-3
Carrier-Free Binary Self-Assembled Nanomedicines Originated from Traditional Herb Medicine with Multifunction to Accelerate MRSA-Infected Wound Healing by Antibacterial, Anti-Inflammation and Promoting Angiogenesis.
International journal of nanomedicine
Background:Deaths from bacterial infections have risen year by year. This trend is further aggravated as the overuse antibiotics and the bacterial resistance to all known antibacterial agents. Therefore, new therapeutic alternatives are urgently needed. Methods:Enlightenment the combination usage of traditional herb medicine, one carrier-free binary nanoparticles (GA-BBR NPs) was discovered, which was self-assembled from gallic acid and berberine through electrostatic interaction, π-π stacking and hydrophobic interaction; and it could be successfully prepared by a green, cost-effective and "one-pot" preparation process. Results:The nanoparticles exhibited strong antibacterial activity and biofilm removal ability against multidrug-resistant (MRSA) by downregulating mRNA expression of and to block bacterial translation mechanisms in vitro and in vivo, and it had well anti-inflammatory activity and a promising role in promoting angiogenesis to accelerate the wound healing on MRSA-infected wounds model in vivo. Additionally, the nanoparticles displayed well biocompatibility without cytotoxicity, hemolytic activity, and tissue or organ toxicity. Conclusion:GA-BBR NPs originated from the drug combination has potential clinical transformation value, and this study provides a new idea for the design of carrier-free nanomedicine derived from natural herbals.
10.2147/IJN.S422944
Multi-functional self-assembly nanoparticles originating from small molecule natural product for oral insulin delivery through modulating tight junctions.
Jia Xiaohui,Yuan Zhihua,Yang Yuqin,Huang Xuemei,Han Nana,Liu Xiaojing,Lin Xiaoyu,Ma Tao,Xu Bing,Wang Penglong,Lei Haimin
Journal of nanobiotechnology
BACKGROUND:Oral administration of insulin (INS) could be absorbed into systemic circulation only if the carrier protected it from the hostile gastrointestinal conditions. However, traditional macromolecular carriers have not totally overcome challenges in addressing these biological barriers. RESULT:In this study, inspired by small molecule natural products (SMNPs), we demonstrate the multi-functional self-assembly nanoparticles (BA-Al NPs) originating from baicalin (BA) and AlCl through coordination bonds and hydrogen bonds. As a novel carrier for oral insulin delivery (INS@BA-Al NPs), it displayed effective capacity in pH stimuli-responsive insulin release, intestinal mucoadhesion and transepithelial absorption enhance. Meanwhile, BA improved the paracellular permeability for insulin absorption, because of its downregulation at both mRNA and protein level on internal tight junction proteins. In vivo experiments exhibited remarkable bioavailability of INS and an ideal glucose homeostasis in the type I diabetic rat model. CONCLUSION:This study offers a novel frontier of multi-functional carriers based on SMNPs with self-assembly character and bioactivity, which could be a promising strategy for diabetes therapy.
10.1186/s12951-022-01260-9
Berberine-Based Heterogeneous Linear Supramolecules Neutralized the Acute Nephrotoxicity of Aristolochic Acid by the Self-Assembly Strategy.
ACS applied materials & interfaces
Aristolochic acid (AA) has been reported to cause a series of health problems, including aristolochic acid nephropathy and liver cancer. However, AA-containing herbs are highly safe in combination with berberine (Ber)-containing herbs in traditional medicine, suggesting the possible neutralizing effect of Ber on the toxicity of AA. In the present study, systematic toxicological experiments performed in zebrafish and mice showed that the supramolecule self-assembly formed by Ber and AA significantly reduced the toxicity of AA and attenuated AA-induced acute kidney injury. Ber and AA can self-assemble into linear heterogenous supramolecules (A-B) via electrostatic attraction and π-π stacking, with the hydrophobic groups outside and the hydrophilic groups inside during the drug combination practice. This self-assembly strategy may block the toxic site of AA and hinder its metabolism. Meanwhile, A-B linear supramolecules did not disrupt the homeostasis of gut microflora as AA did. RNA-sequence analysis, immunostaining, and western blot of the mice kidney also showed that A-B supramolecules almost abolished the acute nephrotoxicity of AA in the activation of the immune system and tumorigenesis-related pathways.
10.1021/acsami.1c06968