The American journal of Chinese medicine
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Andrographolide (APE) has been used for COVID-19 treatment in various clinical settings in South-East Asia due to its benefits on reduction of viral clearance and prevention of disease progression. However, the limitation of APE clinical use is the high incidence of adverse events. The objective of this study was to find the optimal dosage regimens of APE for COVID-19 treatment. ⋯ One hundred virtual populations (50 males and 50 females) were simulated for oral and intravenous infusion formulations of APE. The eligible PBPK/PD models successfully predicted optimal dosage regimens and formulations of APE for prevention of disease progression and/or reduction of viral clearance time. Additionally, APE should be co-administered with other antiviral drugs to enhance therapeutic efficacy for COVID-19 treatment.
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Pulmonary arterial hypertension (PAH) is a malignant cardiopulmonary disease, in which pulmonary arterial remodeling is regarded as the prominent pathological feature. So far, the mechanism of PAH is still unclear, so its treatment remains a challenge. However, inflammation plays an important part in the occurrence and progression of PAH. ⋯ Furthermore, crocin treatment reduced the inflammatory cytokines and oxidative stress responses. In summary, crocin may play a protective role in MCT-induced PAH rats by alleviating inflammatory response, improving pulmonary arterial remodeling, and preventing PAH. Therefore, crocin as a new treatment for PAH may be quite worthy of consideration.
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Dietary capsaicin (CAP), the main irritant component in pepper, can reduce the incidence of diabetes, while metformin (MET) is a first-line oral hypoglycemic drug. The purpose of this study was to investigate whether CAP on the hypoglycemic effect of MET is pertinent to gut microbiota. The glucose and insulin tolerance of diabetic rats were monitored. ⋯ The results showed that CAP and MET co-treatment could significantly reduce fasting blood glucose, improve glucose tolerance, lessen liver injury and inflammatory infiltration, down-regulate inflammatory cytokines and up-regulate intestinal tight junction proteins in diabetic rats by comparing it with MET monotherapy. Moreover, CAP and MET co-treatment altered gut microbiota profiles by regulating microbials' abundances such as Akkermansia. In conclusion, CAP showed the significant hypoglycemic effect of MET and remodulated gut microbiota profiles in diabetic rats.
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Our study aimed to explore the function and mechanism of Dexmedetomidine (Dex) in regulating myocardial ischemia/reperfusion (I/R)-induced mitochondrial apoptosis through lncRNA HCP5. We demonstrated Dex suppressed I/R-induced myocardial infarction and mitochondrial apoptosis in vivo. Dex induced the expression of lncRNA HCP5 and MCL1, inhibited miR-29a expression and activated the JAK2/STAT3 signaling. ⋯ Knockdown of miR-29a also alleviated cardiomyocyte apoptosis by upregulating MCL1. Overexpression of lncRNA HCP5 activated the JAK2/STAT3 signaling through sponging miR-29a and enhancing MCL1 expression in cardiomyocytes. Dex mitigated myocardial I/R-induced mitochondrial apoptosis through the lncRNA HCP5/miR-29a/MCL1 axis and activation of the JAK2/STAT3 signaling.
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Peritoneal fibrosis (PF) is a disease caused by prolonged exposure of the peritoneum to high levels of dialysis fluid. Astragalus total saponins (ATS) is a phytochemical naturally occurring in Radix Astragali that has anti-inflammatory and anti-oxidant properties. In this study, we constructed an in vivo model of PF using 4.25% glucose-containing administered intraperitoneally to rats and incubated peritoneal mesothelial cells (PMCs) with 4.25% glucose-containing peritoneal dialysis fluid to construct an in vitro model of PF. ⋯ ATS treatment also reduced the expressions of peritoneal fibrosis markers (Smad2, p-Smad2 and [Formula: see text]-SMA) and apoptosis markers (Caspase3, cleaved-Caspase3 and Bax) and restored the expressions of mitochondrial synthesis proteins (PGC-1[Formula: see text], NRF1 and TFAM) in ATS-treated peritoneal tissues or PMCs. Furthermore, in the presence of PGC-1[Formula: see text] inhibition, the protective effect of ATS on PF was blocked. In conclusion, ATS treatment may be an effective therapeutic agent to inhibit high glucose-induced in peritoneal fibrosis through PGC-1[Formula: see text]-mediated apoptosis.