Synthesis and biological evaluation of sophocarpinic acid derivatives as anti-HCV agents

Chronic hepatitis C virus(HCV)infection has become a major public health burden worldwide.Twenty-two sophocarpinic acid or matrine derivatives were synthesized and their anti-HCV activities were evaluated in vitro.The structure-activity analysis revealed that(i)sophocarpinic acids with a D-seco 3-ring structure scaffold were more favorable than matrines with a 4-ring scaffold;(ii)the introduction of an electron-withdrawing group on the phenyl ring in 12-N-benzenesulfonylΔβγsophocarpinic acids was beneficial for the antiviral activity against HCV.Among them,compounds 9h and 9j exhibited the most potent inhibitory activities on HCV replication with selectivity indies of 70.3 and 30.9,respectively.Therefore,both were selected as antiviral candidates for further investigation.

Sophocarpine attenuates liver fibrosis by inhibiting the TLR4 signaling pathway in rats

AIM: To explore the effect of sophocarpine on experimental liver fibrosis and the potential mechanism involved.

Quality Standard of Qiang Herb Sophora davidii var.chuansiensis

[Objectives]To establish the quality standard of common clinical folk herb Sophora davidii var.chuansiensis.[Methods]The qualitative identification was performed by microscopic method and thin-layer chromatography(TLC).The contents of moisture,total ash,acid insoluble ash and extract were determined according to the methods of the Chinese Pharmacopoeia(2020).High performance liquid chromatography(HPLC)was used to determine the contents of oxymatrine and oxysophocarpine.[Results]The microscopic characteristics were obvious,including crystal sheath fiber,calcium oxalate square crystal,non glandular hair,stone cells,epidermal cells,stomata,cork cells,vessels with marginal pits and so on.TLC spots were clear,and the resolution was good.The contents of moisture,total ash,acid insoluble ash and extract from 10 batches of samples were 4.70%-8.33%,3.43%-4.19%,0.65%-1.02%and 14.67%-22.04%respectively.The determination results of oxymatrine were between 0.10%-0.33%,with an average value of 0.19%.The determination results of sophocarpine oxide were between 0.30%-0.38%,with an average value of 0.34%.[Conclusions]The established quality standard of S.davidii var.chuansiensis had good specificity and accuracy,and could be used for the quality control of herb S.davidii var.chuansiensis.

PROTECTIVE ROLE OF SOPHOCARPINE IN COXSACKIEVIRUS B3 INFECTION IN CULTURED RAT CARDIOMYOCYTES

Objective To observe the anti-CVB3 （ Coxsackievirus B3 ） effect of sophocarpine （SC） extracted from Sophora flavescens, a traditional Chinese herb in vitro. Methods Cardiomyocytes from the neonatal rat were cultured to establish the viral myocarditis model The cells were divided into four groups： infected group （ infected by CVB3 ） , SC treated group （ added SC 100 μg/mL after viral infection ）, SC control group （ added SC 100 μg/mL only）, and normal control group. The cytopathic effect （CPE） and the beating frequency of the myocardial cells were observed and the LDH levels in the supernatant were measured at day 2,3, and 5. The cultured myocytes were added different concentrations of SC （ 12. 5 -400 μg/mL ） after infection with CVB3, the CPE was observed and the concentrations of LDH were measured and compared at day 2, 3, and 5. Results In the SC treated group （ 100 μg/mL ） , the cytopathic effect was lighter and the LDH level was lower than the infected group. SC in a concentration of 12. 5 - 300 μg/mL could relieve the CPE and lower the LDH level, while in a higher concentration （400 μ/m ） , it exacerbated the CPE caused by the virus, and the LDH levels were higher than the infected cells. Conclusion SC in certain concentration could protect the cultured rat cardiomyocytes from CVB3 infection.

Protection of Sophocarpine on Colonic Barrier in DSS-induced Acute Colitis in Mice by Increasing Expression of HNF4α

Objective To investigate the possible protective effects of sophocarpine on mucosal injury and epithelial barrier disruption on dextran sulfate sodium （DSS）-induced acute colitis. Methods Male BALB/c mice were randomly divided into three groups. The mice in normal group were given normal water, and those in model and sophocarpine- treated groups were given 2.5% DSS for 6 d to induce acute colitis. Sophocarpine （30 mg/kg） was ip administered once daily during the study period. Severity of colitis was evaluated by disease activity index （DAI）, histological injury and inflammatory cytokine production including tumor necrosis factor-α （TNF-α）, interleukin-lβ （IL-Iβ）, and monocyte chemoattractant protein-1 （MCP-1）. The colonic barrier disruption was assessed by testing the expression of junctional adhesion molecule-1 （JAM-1）, E-cadherin （E-CAD）, and desmocollin-2 （DSC-2） in colon mucosa. Expression of HNF4~ in colon mucosa was detected by immunohistochemistry staining and real-time RT-PCR, respectively. Results Compared with normal group, DAI, colonic shortening, and histopathological injury in model group were elevated （P 〈 0.05）, but reduced in sophocarpine-treated group （P 〈 0.05）. Compared with model group, the mRNA expression of inflammatory cytokines （TNF-α, IL-16, MCP-1） were obviously lower in sophocarpine-treated group （P 〈 0.05）, while the cellular junction proteins （E-CAD, JAM-l, and DSC-2） were higher （P 〈 0.05）. The expression of HNF4α at mRNA and protein levels was decreased significantly in model group, but increased apparently in sophocarpine-treated group. Conclusion Sophocarpine can enhance the expression of HNF4α, promote the expression of colonic intrecellular junctions, thus, maintain the integrity of the colonic barrier and inhibit the colitis process. We suggest that sophocarpine could enhance the production of cellular junction proteins to protect the intestinal barrier fuction, at least partly, in HNF4α-dependent pathway.