Physcion, a novel inhibitor of 5α-reductase that promotes hair growth in vitro and in vivo.

Androgenic alopecia (AGA) has a high incidence. Excess dihydrotestosterone in blood capillaries, which is converted from testosterone by 5α-reductase, is an AGA causative factor. We identified the inhibitory activity of four Polygonum multiflorum compounds against 5α-reductase via high-performance liquid chromatography, and the results showed that Physcion was a potent 5α-reductase inhibitor. Additionally, we found that through inhibiting 5α-reductase expression, Physcion could shorten the time of dorsal skin darkening and hair growth, improve hair follicle morphology, and significantly increase hair follicle count. Eventually, through molecular docking study, we found the binding energy and molecular interactions between Physcion and 5α-reductase type II. These results suggested that Physcion is a potent 5α-reductase inhibitor, as well as a new natural medicine for treating AGA.

SanWeiGanJiang San relieves liver injury via Nrf2/Bach1.

ETHNOPHARMACOLOGICAL RELEVANCE: San Wei Gan jiang San (SWGJS) also called Jia Ga Song Tang, is widely used in ancient medicine for liver diseases. THE AIM OF THIS STUDY: To identify the blood components of SWGJS. To determine the hepatoprotective effect and the mechanism of SWGJS by observing its effect on different degrees of liver damage and gene knockdown cells. MATERIALS AND METHODS: SWGJS treated serum was analyzed by UPLC-MS to identify blood components. CCl4-induced chronic liver injury in rats was treated with SWGJS. The viscera index was calculated. Pathological changes of the liver were determined by HE staining and analysis of by following: GSH-Px and MDA in liver homogenate; ALT and AST in serum; mRNA expression of Nrf2, Bach1, and HO-1 by RT-PCR; Nrf2 and Bach1 in the nucleus and cytoplasm; HO-1 total expression by Western blot; silencing Nrf2 and Bach1 in human L-02 cells by siRNA; MDA, GSH-Px, GST, and GR in cell supernatants; and GSH/GSSG within the cell. RESULTS: We found that 6-gingerol was one of the blood components in the serum treated with SWGJS. In CCl4-induced chronic liver injury in rats, SWGJS repaired the liver structure in the early stages of liver damage as evidenced by reduced ALT and AST in the serum, increased GSH-Px activity and decreased MDA levels in the liver over time. SWGJS has excellent antioxidant and hepatoprotective effects and prevents disease progression. The mechanism of SWGJS is related to the dynamics promoting Nrf2 entry to the nucleus and Bach1 exit from the nucleus. In L-02 cells with silenced Nrf2, the antioxidant enzyme system was disordered, and the change in the cellular redox state was not conducive to antioxidative stress. However, in cells with silenced Bach1, the antioxidant enzyme system could be activated to promote cellular antioxidant stress. SWGJS had a combined effect on Nrf2 and Bach1 contributing to antioxidant properties and liver protection. SWGJS increased GSH-Px and HO-1, decreased MDA and increased the ratio of GSH/GSSG by upregulating the expression of Nrf2 to enhance its antioxidant effects. At the same time, SWGJS had a specific impact on decreasing Bach1. Its elevation of GST is due to the overall performance of increasing Nrf2 and decreasing Bach1. This mechanism of action embodies the characteristics of the multitarget impact of traditional medicine and the antioxidation effect of SWGJS. CONCLUSIONS: 6-Gingerol is one of the blood components of SWGJS. SWGJS can regulate antioxidant enzymes, protect against liver damage in different stages, and slow the progression of liver cell damage and liver disease by increasing Nrf2 and reducing Bach1 in the nucleus, dynamically regulating Nrf2/Bach1.

Modification effects of SanWei GanJiang Powder on liver and intestinal damage through reversing bile acid homeostasis.

BACKGROUND: Sanwei Ganjiang Powder (SWGJ), derived from traditional Chinese medicine (TCM), has long demonstrated its effectiveness in long-term liver damage therapy. Recent studies indicated that it can also regulate the intestinal tract, although the underlying molecular mechanisms of this remain mysterious. The aim of the study is to investigate the mechanisms of SWGJ against dysbacteriosis and carbon tetrachloride (CCl4)-induced gut-liver axis damage underlying bile acid enterohepatic circulation. METHODS: To observe the regulatory effects of SWGJ on Liver and Intestinal Damage, we explored two animal models. In model 1, sixty BALB/c mice were subjected to oral gavage with 12 g/kg of ceftriaxone sodium for 10d; during this time, SWGJ, bifendate and bifico were sequentially administered over 7d. In model 2, the model of chronic liver injury was induced by subcutaneous injection of 40% CCl4 oil solution twice per week for 8 weeks. From the 3rd week, SWGJ, bifendate and bifico were sequentially administered for 6 weeks. Intestinal flora (16S rDNA analysis), histology (H&E staining), tight connections (Immunohistochemistry, IHC), ultrastructure (Transmission electron microscopy, TEM), inflammatory cytokines and LPS (Enzyme-linked immunosorbent assay, ELISA) of the intestines were assessed, and liver function was also evaluated by methods including ALT, AST and H&E staining. The levels of protein associated with bile acid metabolism were assessed by western blot. RESULTS: In model 1, SWGJ significantly decreased the activity of inflammatory cytokines and LPS compared with the ceftriaxone sodium group. In addition, SWGJ improved symptoms of intestinal flora imbalance; further, ZO-1 and occludin in the cytoplasm of intestinal villus epithelial cells was increased, and the histopathology of the ileum was improved. Notably, the expression of ALT and AST was significant increased, and disordered hepatic lobule structures were clearly observed in liver histopathology in model group; SWGJ can significantly improve these changes. Furthermore, the levels of proteins related to bile acid synthesis, such as CYP7A1, were significantly upregulated in the SWGJ group compared with the model, and proteins related to excretion and reabsorption, such as NTCP, Mrp2 and BESP, were also upregulated. Importantly, SWGJ increased the nuclear expression of nuclear factor-E2-related factor-2 (Nrf2). Similar results appeared in model 2. CONCLUSION: This study suggests that SWGJ may elicit significant effects on the treatment of gut-liver axis damage, potential mechanisms at least partially involve bile acid enterohepatic, and increasing of the nuclear Nrf2 levels.

Modulation of apoptosis-related microRNAs following myocardial infarction in fat-1 transgenic mice vs wild-type mice.

BACKGROUND: microRNAs (miRNAs) post-transcriptionally regulate cardiac repair following myocardial infarction (MI). Omega-3 polyunsaturated fatty acid (ω-3 PUFAs) may support cardiac healing after MI, but the mechanism is unclear. METHODS: The fat-1 transgenic mouse expresses a ω-3 fatty acid desaturase which converts ω-6 PUFAs to ω-3 PUFAs in vivo. MI was induced in fat-1 transgenic (n = 30) and wild-type (WT) mice (n = 30) using permanent ligation. Other transgenic and WT mice underwent sham procedure (n = 30 and n = 30, respectively). One week after occlusion, cardiac function was measured by echocardiography and the infarct size was assessed using histology and miRNA microarray profiling. Expression of selected miRNA was confirmed using quantitative real-time PCR. RESULTS: One week following MI, the fat-1 transgenic myocardium had better cardiac function, a smaller fibrotic area, and fewer apoptotic cardiomyocytes than WT myocardium. Post-MI profiling showed 33 miRNAs that were significantly up-regulated, and 35 were down-regulated, in fat-1 group compared to the WT group (n = 3 and n = 2 mice, respectively). Among selected apoptosis-associated miRNAs, 9 miRNAs were up-regulated (miR-101a-3p, miR-128-3p,miR-133a-5p,miR-149-5p,miR-192-5p,miR-1a-3p,miR-208a-3p,miR-29c-5p,miR-30c-2-3p), and 3 were down-regulated (miR-210-3p,miR-21a-3p,miR-214-3p) in fat-1 transgenic mice compared with WT mice. Kyoto encyclopaedia of genes and genomes (KEGG) pathway analysis indicated likely roles for these miRNAs in MI. Furthermore, Bcl-2 expression was increased, and caspase-3 decreased, in infarcted fat-1 transgenic mouse hearts compared to WT hearts. CONCLUSIONS: ω-3 PUFAs may have a protective effect on cardiomyocytes following MI through their modulation of apoptosis-related miRNAs and target genes.

Systems pharmacology-based investigation of Sanwei Ganjiang Prescription: related mechanisms in liver injury.

Liver injury remains a significant global health problem and has a variety of causes, including oxidative stress (OS), inflammation, and apoptosis of liver cells. There is currently no curative therapy for this disorder. Sanwei Ganjiang Prescription (SWGJP), derived from traditional Chinese medicine (TCM), has shown its effectiveness in long-term liver damage therapy, although the underlying molecular mechanisms are still not fully understood. To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view, in the present study, a systems pharmacology approach was developed, which involved drug target identification and multilevel data integration analysis. Using a comprehensive systems approach, we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets. We further deciphered the mechanisms of SWGJP in treating liver injury, including compound-target network analysis, target-function network analysis, and integrated pathways analysis. We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway, such as Nrf2-dependent anti-oxidative stress module. Notably, systems pharmacology provides an alternative way to investigate the complex action mode of TCM.