Panlongqi tablet suppresses adjuvant-induced rheumatoid arthritis by inhibiting the inflammatory reponse in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Panlongqi Tablet is prepared with the ancestral secret recipe provided by Mr. Wang Jiacheng, a famous specialist in orthopedics and traumatology of China. The efficacy and safety of PLQT have been supported by years of clinical practice in the treatment of joint-related conditions. Has remarkable effect for treating rheumatoid arthritis (RA) clinically. However, its mechanism is not entirely clear. AIM OF THE STUDY: We aim to evaluate the anti-inflammatory activity of PLQT and explore its mechanism in adjuvant-induced arthritis (AA) mice and LPS-induced Human fibroblast-like synovial (HFLS) cells. MATERIALS AND METHODS: To this end, we analyzed the active ingredients in PLQT by HPLC-MS/MS. Furthermore, the anti-RA effect of PLQT was studied through proliferation, apoptosis, foot swelling, cytokine levels, immune organ index, histopathology and related signal pathways in LPS-induced HFLS cells and AA-treated mice. RESULTS: HPLC-MS/MS results showed that PLQT contained a variety of active compounds, such as epicatechin, imperatorin, hydroxysafflor yellow A and so on. PLQT significantly inhibited the abnormal proliferation of HFLS cells induced by LPS, promoted cell apoptosis. In AA-treated mice, PLQT alleviated RA symptoms by alleviating paw swelling, synovial hyperplasia, pannus formation, inflammatory cell infiltration, and inhibiting abnormal immune responses. The results showed that PLQT significantly decreased the expression of inflammatory mediators (IL-1ß, IL-6, IL-17) in vivo and in vitro, which may be related to the regulation of PI3K/Akt, MAPK and JAK/STAT signaling pathways. CONCLUSION: Based on serum pharmacology and in vivo pharmacology studies, PLQT may regulate RA symptoms by regulating inflammatory and immune response-related pathways, which is an effective method for the treatment of RA.

Immunoenhancement activity of Bletilla striata polysaccharide through MAPK and NF-κB signalling pathways in vivo and in vitro.

Bletilla striata (Thunb.) Reichb.f., is a traditional Chinese medicine, and the Bletilla striata polysaccharide (BSP) is one of the principal components extracted from Bletilla striata with various biological activities. Previous studies have shown that many natural polysaccharides have significant immunomodulatory activities. However, as a plant polysaccharide, the research of BSP on immunomodulatory activities is limited. In this study, we aim to investigate the immunomodulatory effect of BSP in vivo and further explore its underlying mechanism in vitro. In vivo, a cyclophosphamide (CTX)-induced immunosuppression mice mode was established by intraperitoneal injection of CTX, and the immune-enhancing effect of BSP (25, 50 and 100 mg/kg) on immunosuppressed mice were evaluated. The result indicated that BSP could significantly improve the immune organ index and the content of immunoglobulin, TNF-α and IL-4 in serum. It was also found that BSP could clearly ameliorate the spleen damage induced by CTX. Meanwhile, the result showed that BSP could not only improve the proliferation of splenocytes, but also activate the lactate dehydrogenase (LDH) and acid phosphatase (ACP) in mouse spleen tissue. In vitro, potential mechanism was further revealed in macrophages. The result supported that BSP could activate macrophages with high phagocytic ability, and induce macrophages to secrete cytokines. Finally, it revealed that activation of NF-κB and MAPK signalling pathway should be the underlying mechanism of the immunoenhancment of BSP.

Quyu Shengxin capsule (QSC) inhibits Ang-II-induced abnormal proliferation of VSMCs by down-regulating TGF-ß, VEGF, mTOR and JAK-STAT pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Quyu Shengxin capsule (QSC) is an herbal compound commonly used to treat blood stasis syndrome in China, and blood stasis syndrome is considered to be the root of cardiovascular diseases (CVD) in traditional Chinese medicine. However, the potential molecular mechanism of QSC is still unknown. AIM OF STUDY: To study the therapeutic effect of QSC on the abnormal proliferation of VSMCs induced by Ang-II, and to explore its possible mechanism of action. MATERIALS AND METHODS: Qualitative analysis and quality control of QSC through UPLC-MS/MS and UPLC. The rat thoracic aorta vascular smooth muscle cells (VSMCs) were cultured in vitro, and then stimulated with Angiotensin Ⅱ (Ang-II) (10-7 mol/L) for 24 h to establish a cardiovascular cell model. The cells were then treated with different concentrations of QSC drug-containing serum or normal goat serum. MTT assay was used to detect the viability of VSMCs and abnormal cell proliferation. In order to analyze the possible signal transduction pathways, the content of various factors in the supernatant of VSMCs was screened and determined by means of the Luminex liquid suspension chip detection platform, and the phosphoprotein profile in VSMCs was screened by Phospho Explorer antibody array. RESULTS: Compared with the model group, serum cell viability and inflammatory factor levels with QSC were significantly decreased (P < 0.001). In addition, the expression levels of TGF-ß, VEGF, mTOR and JAK-STAT in the QSC-containing serum treatment group were significantly lower than those in the model group. QSC may regulate the pathological process of CVD by reducing the levels of inflammatory mediators and cytokines, and protecting VSMCs from the abnormal proliferation induced by Ang-II. CONCLUSION: QSC inhibits Ang-II-induced abnormal proliferation of VSMCs, which is related to the down-regulation of TGF-ß, VEGF, mTOR and JAK-STAT pathways.

Structure and Anti-HIV Activity of Betulinic Acid Analogues.

Firstly discovered in 1980s, human immunodeficiency virus (HIV) continues to affect more and more people. However, there is no effective drug available for the therapy of HIV infection. Betulinic acid existing in various medicinal herbs and fruits exhibits multiple biological effects, especially its outstanding anti-HIV activity, which has drawn the attentions of many pharmacists. Among the derivatives of betulinic acid, some compounds exhibited inhibitory activities at the nanomolar concentration, and have entered phase II clinical trials. This paper summarizes the current investigations on the anti-HIV activity of betulinic acid analogues, and provides valuable data for subsequent researches.

Anti-hepatocellular carcinoma activity and mechanism of chemopreventive compounds: ursolic acid derivatives.

CONTEXT: Hepatocellular carcinoma (HCC) is a common cancer around the world, with high mortality rate. Currently, there is no effective drug for the therapy of HCC. Ursolic acid (UA) is a natural product which exists in various medicinal herbs and fruits, exhibiting multiple biological effects such as its outstanding anticancer and hepatoprotective activity, which has drawn many pharmacists' attention. OBJECTIVE: This paper summarizes the current status of the hepatoprotective activity of UA analogues and explains the related mechanism, providing a clear direction for the development of novel anti-HCC drugs. METHODS: All of the data resources were derived from PubMed. By comparing the IC50 values and analyzing the structure-activity relationships, we listed compounds with good pharmacological activity from the relevant literature, and summarized their anti-HCC mechanism. RESULTS: From the database, 58 new UA derivatives possessing wonderful anticancer and hepatoprotective effects were listed, and the relevant anti-HCC mechanism were discussed. CONCLUSION: UA's anti-HCC effect is the result of combined action of many mechanisms. These 58 new UA derivatives, particularly compounds 45 and 53, can be used as potential drugs for the treatment of liver cancer.