Guizhou Bailing Group Pharmaceutical Co., Ltd.

Sabia parviflora (SP, "xiao hua qing feng teng" in Chinese) was recorded as an important ethnic medicine to be used for treating viral hepatitis. The antiviral activity of four SP extracts and potent antiviral compounds evaluated with cathepsin L protease (Cat L PR) and HIV-1 protease (HIV-1 PR). UPLC-HRMS was used for identifying the bioactive components. In addition, the possible inhibitory mechanism of the identified compounds on viral protease was further discussed by molecular docking. As a result, four extracts of SP exhibited inhibitory activity of HIV-1 PR and Cat L PR with IC₅₀ range from 0.015 to 0.80 mg/mL. Meanwhile, six compounds inhibited HIV-1 PR with IC₅₀ range from 0.032 to 0.80 mg/mL. Moreover, procyanidin B2 had good affinity for HIV-1 PR and CatL PR protein, respectively. These findings suggest S. parviflora leaves can be used for treating HIV and procyanidin B2 may play a role in antiviral protease.

With increasing stress in daily life and work, subhealth conditions induced by "Shi-Re Shanghuo" syndrome was gradually universal. "Huanglian Jiedu Wan" (HLJDW) was the first new syndrome Chinese medicine approved for the treatment of "Shi-Re Shanghuo" with promising clinical efficacy. Preliminary small-sample clinical studies have identified some notable biomarkers (succinate, 4-hydroxynonenal, etc.). However, the correlation and underlying mechanism between these biomarkers of HLJDW intervention on "Shi-Re Shanghuo" syndrome remained ambiguous. Therefore, this study was designed as a randomized, double-blind, multicenter, placebo-controlled Phase II clinical trial, employing integrated analysis techniques such as non-targeted and targeted metabolomics, salivary microbiota, proteomics, parallel peaction monitoring, molecular docking and surface plasmon resonance (SPR). The results of the correlation analysis indicated that HLJDW could mediate the balance between inflammation and immunity through succinate produced via host and microbial source to intervene "Shi-Re Shanghuo" syndrome. Further through the HIF1α/MMP9 pathway, succinate regulated downstream arachidonic acid metabolism, particularly the lipid peroxidation product 4-hydroxynonenal. Finally, an animal model of recurrent oral ulcers induced by "Shi-Re Shang Huo" was established and HLJDW was used for intervention, key essential indicators (succinate, glutamine, 4-hydroxynonenal, arachidonic acid metabolism) essential in the potential pathway HIF1α/MMP9 discovered in clinical practice were validated. The results were found to be consistent with our clinical findings. Taken together, succinate was observed as an important signal that triggered immune responses, which might serve as a key regulatory metabolic switch or marker of "Shi-Re Shanghuo" syndrome treated with HLJDW.