The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective: To investigate the effects of buccal acupuncture on analgesia, immune indicators, and expression levels of Survivin and Livin proteins in patients with advanced-stage primary liver cancer. Methods: Eighty patients with advanced-stage primary liver cancer were selected and divided into control and treatment groups according to the difference in treatment modalities, with 40 patients in each group. The control group received transcatheter arterial chemoembolization (TACE), and the treatment group received buccal acupuncture in addition to TACE. The recent efficacy, analgesic effect, liver function, serum tumor markers, Survivin and Livin protein expression levels in liver cancer tissue, and immune indexes were analyzed and compared between the two groups. Results: The objective response rate (ORR) and disease control rate (DCR) of the treatment group were 37.5％ and 77.5％, respectively, which were significantly higher than those of the control group (22.5％ and 52.5％), and the recent efficacy of the treatment group was significantly better than that of the control group (P<0.05). The onset of analgesia in the treatment group was significantly faster than that in the control group (P<0.05), the duration of analgesia was significantly longer than that in the control group (P<0.05), and the numeric rating scale (NRS) score of pain after treatment was significantly lower than that in the control group (P<0.05). In the treatment group, the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin/globulin (A/G) were significantly lower than those in the control group (P<0.05), and the serum levels of alpha-fetoprotein (AFP), alpha-L-fucosidase (AFU), and carcinoembryonic antigen (CEA) were significantly lower than those in the control group (P<0.05), and the expression levels of Survivin and Livin in liver cancer tissue were significantly lower than those in the control group (P<0.05); CD4+ and CD4+/CD8+ in the treatment group were significantly higher than those in the control group, and CD8+ was significantly lower than that in the control group after treatment (P<0.05). Conclusion: Buccal acupuncture can reduce the degree of pain and liver function damage in patients with advanced- stage primary liver cancer and lower the serum tumor marker levels, and its mechanism of action may be related to the down-regulation of Survivin and Livin protein expression levels in the liver cancer tissue and the regulation of the immune function.