The important herbal pair for the treatment of COVID-19 and its possible mechanisms.
Xia Shujie,Zhong Zhangfeng,Gao Bizhen,Vong Chi Teng,Lin Xuejuan,Cai Jin,Gao Hanlu,Chan Ging,Li Candong
BACKGROUND:Coronavirus Disease 2019 (COVID-19) is an unprecedented disaster for people around the world. Many studies have shown that traditional Chinese medicine (TCM) are effective in treating COVID-19. However, it is difficult to find the most effective combination herbal pair among numerous herbs, as well as identifying its potential mechanisms. Herbal pair is the main form of a combination of TCM herbs, which is widely used for the treatment of diseases. It can also help us to better understand the compatibility of TCM prescriptions, thus improving the curative effects. The purpose of this article is to explore the compatibility of TCM prescriptions and identify the most important herbal pair for the treatment of COVID-19, and then analyze the active components and potential mechanisms of this herbal pair. METHODS:We first systematically sorted the TCM prescriptions recommended by the leading experts for treating COVID-19, and the specific herbs contained in these prescriptions across different stages of the disease. Next, the association rule approach was employed to examine the distribution and compatibility among these TCM prescriptions, and then identify the most important herbal pair. On this basis, we further investigated the active ingredients and potential targets in the selected herbal pair by a network pharmacology approach, and analyzed the potential mechanisms against COVID-19. Finally, the main active compounds in the herbal pair were selected for molecular docking with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) 3CLpro and angiotensin converting enzyme II (ACE2) for further verification. RESULT:We obtained 32 association rules for the herbal combinations in the selection of TCM treatment for COVID-19. The results showed that the combination of Amygdalus Communis Vas (ACV) and Ephedra sinica Stapf (ESS) had the highest confidence degree and lift value, as well as high support degree, which can be used in almost all the stages of COVID-19, so ACV and ESS (AE) were selected as the most important herbal pair. There were 26 active ingredients and 44 potential targets, which might be related to the herbal pair of AE against COVID-19. The main active ingredients of AE against COVID-19 were quercetin, kaempferol, luteolin, while the potential targets were Interleukin 6 (IL-6), Mitogen-activated Protein Kinase 1 (MAPK)1, MAPK8, Interleukin-1β (IL-1β), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) p65 subunit (RELA). The protein-protein interaction (PPI) cluster demonstrated that IL-6 was the seed in the cluster, which plays an important role in connecting other nodes in the PPI network. The potential pathways mainly involved tumor necrosis factor (TNF), Toll-like receptor (TLR), hypoxia-inducible factor-1 (HIF-1), and nucleotide-binding oligomerization domain (NOD)-like receptor (NLRs). The molecular docking results showed that the main active ingredients of AE have good affinity with SARS-COV-2 3CLpro and ACE2, which are consistent with the above analysis. CONCLUSIONS:There were 32 association rules in the TCM prescriptions recommended by experts for COVID-19. The combination of ACV and EAS was the most important herbal pair for the treatment of COVID-19. AE might have therapeutic effects against COVID-19 by affecting the inflammatory and immune responses, cell apoptosis, hypoxia damage and other pathological processes through multiple components, targets and pathways.
attenuates streptozotocin induced diabetic cardiomyopathy via inhibition of oxidative stress and inflammatory response in rats.
Sharma Manju,Afaque Aiman,Dwivedi Shridhar,Jairajpuri Zeeba S,Shamsi Yasmeen,Khan Mohd Faiyaz,Khan Mohd Ibrahim,Ahmed Danish
The aim of the present study was to investigate the effects of on lipid peroxidation activities of both enzymatic and non-enzymatic antioxidants, inflammatory mediators, myocardial enzymes and histopathology of cardiac tissues in experimental diabetic cardiomyopathy (DCM). DCM was induced by single intraperitoneal injection of streptozotocin (STZ) (40 mg/kg) combined with high energy intake in rats. Seed extract of (CIE) (250 mg/kg & 500 mg/kg) was administered orally once a day for 3 weeks. Phytochemical investigations of seed extract revealed presence of some active ingredients such as alkaloids, tannins, saponin, phenols, glycosides, steroids, terpenoids and flavonoids. Seed extract of confirmed a significant potency towards restoring the blood glucose, an elevation of the levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), blood glutathione (GSH), TNF-α and IL-6 and a reduction in the levels of catalase (CAT) was observed following the STZ treatment. Oxidative stress was accompanied by myocardial degeneration as evidenced by histopathological examination of cardiac tissues. Administration of CIE reduced the lipid peroxides level in heart. Serum levels of AST, GSH, LDH and SOD were brought down to physiological levels by CIE in STZ induced DCM rats. CIE also markedly down-regulated serum TNF-α and IL-6 levels. Catalase that was reduced in serum was brought back to near normal level. The extensive necrotic changes of cardiac tissue by STZ was minimized to normal morphology upon CIE administration. The study demonstrates the cardioprotective effect of CIE via inhibition of oxidative stress and pro-inflammatory cytokines.