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Oridonin is the primary active component in the traditional Chinese medicine Rabdosia rubescens, displaying anti-inflammatory, anti-tumor, and antibacterial effects. It is widely employed in clinical therapy for acute and chronic pharyngitis, tonsillitis, as well as bronchitis. Nevertheless, the clinical application of oridonin is significantly restricted due to its reproductive toxicity, with the exact mechanism remaining unclear. The aim of this study was to investigate the mechanism of oridonin-induced damage to HTR-8/SVneo cells. Through the integration of epigenetics, proteomics, and metabolomics methodologies, the mechanisms of oridonin-induced reproductive toxicity were discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that oridonin altered m6A levels, gene and protein expression levels, along with metabolite levels within the cells. Additionally, oridonin triggered oxidative stress and mitochondrial damage, leading to a notable decrease in WNT6, β-catenin, CLDN1, CCND1, and ZO-1 protein levels. This implied that the inhibition of the Wnt/β-catenin signaling pathway and disruption of tight junction might be attributed to the cytotoxicity induced by oridonin and mitochondrial dysfunction, ultimately resulting in damage to HTR-8/SVneo cells. [ABSTRACT FROM AUTHOR]

Objective: To systematically review the clinical efficacy and safety of Chinese herbal medicine (CHM) with and without Western medicine (WM) for different severity of COVID-19. Methods: CNKI, PubMed, Wanfang Database, ClinicalTrails.gov, Embase, ChiCTR and ICTRP were searched from 01 Jan, 2020 to 30 Jun, 2021. Two authors independently assessed all the randomized clinical trials (RCTs) for trial inclusion, data extraction and quality assessment. Meta-analysis was conducted using Review Manager software (RevMan 5.4.1). Evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Primary outcomes included total effectiveness rate. Secondary outcomes included improvements in symptom improvement and total adverse event rate. Different severity of COVID-19 patients was assessed in subgroup analysis. This study was registered with INPLASY, INPLASY202210072. Results: 22 high quality RCTs involving 1789 participants were included. There were no trial used CHM alone nor compare placebo or no treatment. Compared with WM, combined CHM and WM (CHM-WM) treatment showed higher total effectiveness rate, lower symptom scores of fever, cough, fatigue, dry throat and pharyngalgia, shorter mean time to viral conversion, better Computerized Tomography (CT) image and blood results, fewer total adverse events and worse conditions (P < 0.05). Subgroup analysis showed that the total effectiveness rate of combined CHM-WM group was significantly higher than WM group, especially for mild and moderate patients. No significant differences in mortality and adverse events were found between combined CHM-WM and WM treatment. No serious adverse events and long-term outcomes were reported. Conclusion: Current evidence supported the therapeutic effects and safety of combined CHM-WM treatment on COVID-19, especially for patients with mild and moderate symptoms. Long-term effects of therapy are worthy in further study. [ABSTRACT FROM AUTHOR]

Bronchitis is a respiratory disease characterized by a productive cough. Polygala tenuifolia Willd., commonly known as Yuan zhi , is a traditional Chinese herbal medicine used for relieving cough and removing phlegm. Despite its historical use, studies are lacking on the effectiveness of P. tenuifolia in treating bronchitis. Furthermore, the molecular mechanisms underlying the action of its bioactive compounds remain unknown. This study aims to identify the main bioactive compounds responsible for the effects of P. tenuifolia liquid extract (PLE) in treating bronchitis and to elucidate the associated molecular mechanisms. The main chemical compounds in PLE were identified and determined using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The antitussive, expectorant and anti-inflammatory activities of PLE were evaluated in an ammonia-induced mouse cough model, a tracheal phenol red excretion mouse model, and a xylene-induced ear swelling mouse model, respectively. A network pharmacology analysis was conducted to investigate the associated gene targets, gene ontology, and KEGG pathways related to the main bioactives in PLE targeting bronchitis. PLE and its five bioactive compounds were assessed for their potential anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Western blot analysis was conducted to elucidate the associated molecular mechanisms. Thirty-seven compounds in PLE were identified, and twelve main compounds were further quantified in PLE using UPLC-MS/MS. PLE oral gavage administrations (0.6 and 0.12 mg/kg) for 7 days markedly reduced cough frequency, prolonged latency period of cough, reduced phlegm and inflammation in mice. The network pharmacology analysis identified 57 gene targets of PLE against bronchitis. The PI3K/AKT and MAPK signalling pathways were the top two modulated pathways. In RAW264.7 cells, PLE (12.5–50 μg/mL) significantly reduced cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. PLE downregulated LPS-elevated protein targets in both PI3K/AKT and MAPK signaling pathways. In PLE, tenuifolin, polygalaxanthone ⅠⅠⅠ, polygalasaponin ⅩⅩⅤⅢ, tenuifoliside B, and 3,6′-Disinapoyl sucrose, were identified as the top five core components responsible for treating bronchitis. These compounds were also found to modulate the protein targets in the PI3K/AKT and MAPK signalling pathways. This study demonstrated the potential therapeutic effects of PLE on bronchitis by reducing cough, phlegm and inflammation. The anti-inflammatory action and molecular mechanisms of the 5 main bioactive compounds in PLE were partly validated through the in vitro assays. The findings provide valuable insights into the mechanisms underlying the traditional use of PLE for bronchitis. [Display omitted] • New UPLC-MS/MS method validated for PLE chemical composition. • PLE reduced cough frequency, phlegm and inflammation in mice. • PLE modulated the PI3K/AKT and MAPK pathways against bronchitis. • Five bioactive compounds identified in PLE against bronchitis. • These compounds modulated protein targets in PI3K/AKT and MAPK pathways. [ABSTRACT FROM AUTHOR]

Aidi injection (ADI) is a popular anti-tumor Chinese patent medicine, widely used in clinics for the treatment of hepatocellular carcinoma (HCC) with remarkable therapeutic effects through multiple targets and pathways. However, the scientific evidence of the synergistic role of the complex chemical component system and the potential mechanism for treating diseases are ignored and remain to be elucidated. This study aimed to elucidate and verify the cooperative association between the potential active ingredient of ADI, which is of significance to enlarge our understanding of its anti-HCC molecular mechanisms. Firstly, the anti-HCC effect of ADI was evaluated in various HCC cells and the zebrafish xenograft model. Subsequently, a variety of bioinformatic technologies, including network pharmacology, weighted gene co-expression network analysis (WGCNA), meta-analysis of gene expression profiles, and pathway enrichment analysis were performed to construct the competitive endogenous RNA (ceRNA) network of ADI intervention in HCC and to establish the relationship between the critical targets/pathways and the key corresponding components, which were involved in ADI against HCC in a synergistic way and were validated by molecular biology experiments. ADI exerted remarkable anti-HCC in vitro cells and in vivo zebrafish model, especially that the Hep 3B2.1-7 cell showed substantial sensibility to ADI. The ceRNA network revealed that the EGFR/PI3K/AKT signaling pathway was identified as the promising pathway. Furthermore, the meta-analysis also demonstrated the critical role of BIRC5 and FEN1 as key targets. Finally, the synergistic effect of ADI was revealed by discovering the inhibitory effect of cantharidin on BIRC5, formononetin on FEN1 and EGFR, as well as isofraxidin on EGFR. Our study unveiled that the incredible protective effect of ADI on HCC resulted from the synergistic inhibition effect of cantharidin, formononetin, and isofraxidin on multiple targets/pathways, including BIRC5, FEN1, and EGFR/PI3K/AKT, respectively, providing a scientific interpretation of ADI against HCC and a typical example of pharmacodynamic evaluation of other proprietary Chinese patent medicine. [Display omitted] • Systematically elucidated the role of ADI in the regulation of ncRNA in HCC. • Proved the synergistic effect of multiple components and pathways of ADI against HCC. • Established and confirmed the correspondence between components and targets in ADI. [ABSTRACT FROM AUTHOR]

Pien Tze Huang is a classic traditional Chinese medicinal product, used for inflammatory diseases as stated in Chinese Pharmacopoeia. In particular, it is effective in treating liver diseases and pro-inflammatory conditions. Acetaminophen (APAP) is a widely used analgesic drug, but its over-dose is associated with acute liver failure where the clinical approved antidote treatment is limited. Inflammation has been considered as one of the therapeutic targets against APAP-induced liver injury. We aimed to explore the therapeutic potential of Pien Tze Huang tablet (PTH) on protecting liver against APAP-induced liver injury through its strong anti-inflammatory pharmacological action. Wild-type C57BL/6 mice were given PTH (75, 150 and 300 mg/kg) by oral gavage 3 days before the APAP injection (400 mg/kg). The protective effect of PTH was assessed by aspartate aminotransferase (AST) and alanine transaminase (ALT) levels and pathological staining. The mechanisms underlying PTH's hepatoprotective effects were investigated in nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) knock-out (NLRP3−/−), over expression NLRP3 (oe-NLRP3) mice, and wild-type mice with the injection of autophagy inhibitor (3-methyladenine, 3-MA). APAP-exposed mice resulted in evident liver injury which was evidenced by hepatic necrosis and elevated levels of AST and ALT in the wild-type C57BL/6 mice. PTH dose-dependently reduced ALT, AST and upregulated autophagy activity. In addition, PTH significantly reduced elevated levels of proinflammatory cytokines and NLRP3 inflammasome. The liver protective effect of PTH (300 mg/kg) was still obvious in the oe-NLRP3 mice, however, it became insignificant in the NLRP3−/− mice. When PTH (300 mg/kg) was co-treated with 3-MA to the wild-type C57BL/6 mice, the NLRP3 inhibition were reversed when autophagy was blocked. PTH exerted a beneficial effect in protecting liver against APAP-induced liver injury. The underlying molecular mechanism was associated with the NLRP3 inflammasome inhibition which was likely driven by the upregulated autophagy activity. Our study underpins the traditional use of PTH in protecting liver through its anti-inflammatory action. [Display omitted] • Pien Tze Huang tablet (PTH) protected liver against acetaminophen-induced liver injury. • PTH suppressed liver inflammation induced by overdose acetaminophen. • The antidote mechanism is associated with nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome inhibition. • PTH's NLRP3 inhibition was driven by the upregulated autophagy. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Fufangkushen colon-coated capsule (FCC) was a newly developed herbal drug for treating ulcerative colitis (UC) patients with traditional Chinese medicine (TCM) pattern of damp-heat accumulating in the interior. Objective: To explore the efficacy and safety of FCC in the treatment of active UC compared with Huidi (HD, mesalazine enteric-coated tablets) were evaluated in a double-blinded and randomized clinical trial. Materials and Methods: In the double-blind, double-dummy, multicenter, randomized and controlled study, 320 active UC patients with TCM pattern of damp-heat accumulating in the interior were assigned to two groups: 240 treated with FCC plus HD placebo treatment, 80 with HD plus FCC placebo. The drugs and their corresponding placebos were administrated at advised dosage for 8 weeks. The primary endpoint was a positive clinical response at week 8, and Mayo scoring system was employed for assessment of UC activity. Results: At the 8th week, 72.50% of patients in FCC group (170 of 234) and 65.00% of patients in HD group (52 of 80) had achieved a clinical response. There was no statistically significance between the 2 groups (P >0.05). The proportions of patients who had a clinical remission was similar in 2 groups (41.50% in FCC group, 41.25% in HD group, P >0.05), mucosal healing rate at week 8 in the two groups were also without significant difference (55.13% in FCC group, 55.00% in HD group, P >0.05). Mayo scores at week 8 showed no statistically difference in the two groups. No significant differences were observed between the safety profiles of the 2 groups (P >0.05). No severe AEs were reported in either group. The latent class analysis indicated that FCC was superior applicable for the left hemicolon involved patients than HD. Conclusions: Compared with HD, a mesalamine enteric-coated tablet, FCC is similarly effective and safe in the treatment of active UC with TCM pattern of damp-heat accumulation interior pattern. In addition, FCC indicates superior effect in the treatment of UC with inflamed area of the left hemicolon than HD. [Copyright &y& Elsevier]