[Effect of electroacupuncture on pain threshold and expression of pain-related factors cyclooxygenase-2, prostaglandin E2 and ß-endorphin in rats with chronic pelvic pain syndrome].

OBJECTIVE: To explore the possible mechanism of electroacupuncture (EA) underlying improvement of chronic pelvic pain syndrome (CPPS). METHODS: Fifty SD rats were randomly divided into control, model, sham operation, EA and sham EA groups (n=10 rats in each group). The CPPS model was established by injecting complete Freund's adjuvant (CFA, 50 µL) into the ventral lobes of the prostate. EA (2 Hz/100 Hz) was applied to "Guanyuan"(CV4), "Zhongji"(CV3), "Sanyinjiao" (SP6) and "Huiyang"(BL35) once daily for 40 min, 5 days a week for 4 weeks, while rats in the sham EA group were treated with the same acupoints but without electrical stimulation. Mechanical pain threshold (MPT) and heat pain threshold (HPT) were measured before and after intervention. The body weight and prostate weight were measured and prostate index was calculated. Histopathological changes of prostate tissue were observed by HE staining. The levels of cycloxygenase-2 (COX-2), prostaglandin E2 (PGE2) and ß-endorphin (ß-EP) in prostate tissue were detected by ELISA. RESULTS: Compared with the control and sham operation groups, the MPT and HPT were significantly lower (P<0.01), and the prostate weight, prostate index, the contents of PGE2 and COX-2 were significantly increased (P<0.01), while the content of ß-EP was significantly decreased (P<0.01) in the model group. Compared with the model group, the MPT and HPT were significantly increased (P<0.01) after 3 and 4 courses of treatment, and the prostate weight, prostate index, the contents of PGE2 and COX-2 were significantly decreased (P<0.01), while the content of ß-EP was significantly increased (P<0.01) in the EA group, rather than in the sham EA group (P>0.05). CONCLUSION: EA can effectively relieve pain in CPPS rats, which may be related to its functions in down-regulating COX-2 and PGE2, and up-regulating ß-EP.

Anti-inflammatory effect of Kaba Sura Kudineer (AYUSH approved COVID-19 drug)-A Siddha poly-herbal formulation against lipopolysaccharide induced inflammatory response in RAW-264.7 macrophages cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal importance and potential activity of Siddha herbal formulations have proved over several centuries against a wide range of causative agents as Influenza, Dengue, Chikungunya, and Tuberculosis. The traditional medicine system of Siddha is a valuable therapeutic approach for treating viral respiratory infections like Coronavirus disease 2019 (COVID-19) and can be effectively employed to target the host response and preventive care to boost the immune system. Kaba Sura Kudineer (KSK), an official polyherbal formulation has been used in Siddha traditional medicine for centuries. However, the role of KSK in regulating inflammation and the underlying molecular mechanisms has remained elusive. AIM OF THE STUDY: The goal of this study was to evaluate the anti-inflammatory effect of KSK using lipopolysaccharide (LPS) stimulated RAW 264.7 murine macrophage cells. MATERIALS AND METHODS: Raw 264.7 murine macrophage cells were used for this study. The Inflammatory mediators and cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The NF-κB nulcear translocation and protein expression of iNOS, COX-2 was analyzed with westernblot. RESULTS: KSK supplementation decreased LPS mediated TLR-4 production and secretion of pro-inflammatory mediators and cytokines including IL-6, TNF-α, COX-2 and PGE-2. Moreover, it inhibited the production of nitric oxide (NO) and thereby inhibited the expression of iNOS in the cell. The Western blot analysis further confirmed that KSK strongly prevented the LPS-induced degradation of IκB which is normally required for the activation of NF-κB and hereby suppressed nuclear translocation of NF-κB. The protein expression of iNOS, COX-2 was significantly decreased with the presence of KSK treatment. Results suggested that KSK manipulates its anti-inflammatory effects mainly through blocking the TLR mediated NF-κB signal transduction pathways. CONCLUSIONS: Together, this study has proven that KSK could be a potential therapeutic drug for alleviating excessive inflammation in many inflammation-associated diseases like COVID-19.

The antifibrotic and fibrolytic properties of date fruit extract via modulation of genotoxicity, tissue-inhibitor of metalloproteinases and nuclear factor- kappa B pathway in a rat model of hepatotoxicity.

BACKGROUND: Hepatic fibrosis and its end point; cirrhosis, are the major cause of liver failure and death in patients with chronic liver disease. Therefore, the need for an effective treatment is evident. This study was designed to assess the potential effects of aqueous extract of date fruits, either flesh (DFE) or pits (DPE), on oxidative DNA damage and liver inflammation induced by carbon tetrachloride (CCl4) and whether they are related to inhibition of nuclear factor-κB pathway. In addition, the fibrolytic potential was evaluated via measuring matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases -1 and -2. METHODS: Rats were divided into the following groups: normal control, model control (CCl4 only), CCl4 + DFE, CCl4 + DPE and CCl4 + coffee. Coffee was used as a positive control. Fibrosis was induced by chronic administration of CCl4 (0.4 ml/kg) 3× a week for 8 weeks, and rats were treated with 6 ml/kg/day of DFE or DPE for 8 weeks. Liver homogenate was prepared for evaluation of oxidative stress, DNA damage, inflammatory and fibrolytic markers. Data are analyzed using one-way analysis of variance followed by a Tukey-Kramer post hoc test. RESULTS: Both DFE and DPE significantly attenuated CCl4-induced oxidative damage as indicated by reducing lipid, protein and DNA oxidation in addition to increasing the levels of hepatic catalase activity. Both extracts blocked the accumulation of collagen I in the liver and ameliorated the increased expression of collagen III and α-smooth muscle actin suggesting suppression of profibrotic response induced by CCl4. DFE and DPE also upregulated the expression of heme oxygenase-1 and attenuated the nuclear factor-κB activation and cycloxygenase-2 expression reflecting their anti-inflammatory potential. Additionally, both flesh and pits extracts attenuated the increase in the tissue inhibitor of metalloproteinases -1 and -2 suggesting their fibrolytic activity. CONCLUSION: Our data suggest that DFE or DPE can prevent liver fibrosis by suppressing genotoxicity and nuclear factor-κB inflammatory pathway and by promoting collagen degradation.

Combination use of ferulic acid, ligustrazine and tetrahydropalmatine inhibits the growth of ectopic endometrial tissue: a multi-target therapy for endometriosis rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ferulic acid (FA), ligustrazine (LZ) and tetrahydropalmatine (THP) are separately isolated from Chinese Angelica, Szechwan Lovage Rhizome and Rhizoma in the Jiawei-Foshou-San formula, a popular traditional Chinese medicine for irregular menses. It has been reported that the combination use of FA+LZ+THP has similar effect on endometriosis, but the underlying mechanisms are unclear. This study was to investigate the combination effects and mechanisms of FA+LZ+THP on endometriosis rats. MATERIALS AND METHODS: Fifty endometriosis rats were intragastricly treated with FA+LZ+THP for 4 wk. The volume of ectopic endometrial tissue was measured to evaluate the effects. Then the changes in hypothalamic-pituitary-ovarian axis and ERE pathway were indicated by the levels of E2, GnRH, FSH and LH, and the expressions of ER, HSP90 and COX-2, respectively. In addition, peritoneal macrophages of each rat were cultured in vitro and treated with (FA+LZ+THP)-medicated serum for 24h. The proliferation and phagocytosis abilities, the levels of IL-1ß and TNF-α, and the expression of IκBα were then measured for the changes of peritoneal macrophage activities. RESULTS: Combination use of FA+LZ+THP diminished the volume of the ectopic endometrial tissues (P<0.05 or P<0.01). It also decreased the E2 level, suppressed the expression of GnRH, FSH and LH, and decreased the protein expression of ER, HSP90 and COX-2 (all P<0.05 or P<0.01). The phagocytosis ability of peritoneal macrophage was enhanced by (FA+LZ+THP)-medicated serum (P<0.05) with no change of proliferation (P>0.05). Moreover, IL-1ß and TNF-α were downregulated (both P<0.05 or P<0.01) and IκBα was upregulated by the (FA+LZ+THP)-medicated serum (P<0.01). CONCLUSIONS: The combination use of FA, LZ and THP could inhibit the growth of ectopic endometrial tissue in endometriosis rats. It might be related to the down-regulation of hypothalamic-pituitary-ovarian axis, the amelioration in ERE pathway and the improvement of peritoneal macrophage activities.