Anti-inflammatory effects of Tao Hong Si Wu Tang in mice with lung cancer and chronic obstructive pulmonary disease.

BACKGROUND: Lung cancer (LC) combined with chronic obstructive pulmonary disease (COPD) is a common combination of comorbidities. Anti-inflammation and modulation of oxidative/antioxidative imbalance may prevent COPD-induced LC, and are also crucial to the treatment of LC combined with COPD. Modern studies have shown that Tao Hong Si Wu Tang (THSW) has vasodilatory, anti-inflammatory, anti-fatigue, anti-shock, immunoregulatory, lipid-reducing, micronutrient-supplementing, and anti-allergy effects. AIM: To observe the effects of THSW on COPD and LC in mice. METHODS: A total of 100 specific pathogen-free C57/BL6 mice were randomly divided into five groups: Blank control group (group A), model control group (group B), THSW group (group C), IL-6 group (group D), and THSW + IL-6 group (group E), with 20 mice in each group. A COPD mouse model was established using fumigation plus lipopolysaccharide intra-airway drip, and an LC model was replicated by in situ inoculation using the Lewis cell method. RESULTS: The blank control group exhibited a clear alveolar structure. The model control and IL-6 groups had thickened alveolar walls, with smaller alveolar lumens, interstitial edema, and several inflammatory infiltrating cells. Histopathological changes in the lungs of the THSW and THSW + IL-6 groups were less than those of the model control group. The serum IL-1ß, IL-6, and TNF-α levels and IL-6R, JAK, p-JAK, STAT1/3, p-STAT1/3, FOXO, p-FOXO, and IL-7R expression levels in lung tissues of mice in the rest of the groups were significantly higher than those of the blank control group (P < 0.01). Compared with the model control group, the IL-6 group demonstrated significantly higher levels for the abovementioned proteins in the serum and lung tissues (P < 0.01), and the THSW group had significantly higher serum IL-1ß, IL-6, and TNF-α levels and IL-7R expression levels in lung tissues (P < 0.01) but significantly decreased IL-6R, JAK, p-JAK, STAT1/3, p-STAT1/3, FOXO, p-FOXO, and IL-7R levels (P < 0.01). CONCLUSION: THSW reduces the serum IL-1ß, IL-6, and TNF-α levels in the mouse model with anti-inflammatory effects. Its anti-inflammatory mechanism lies in inhibiting the overactivation of the JAK/STAT1/3 signaling pathway.

Tao-Hong-Si-Wu-Tang improves thioacetamide-induced liver fibrosis by reversing ACSL4-mediated lipid accumulation and promoting mitophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is a generic fibrous scarring event resulting from accumulation of extracellular matrix (ECM) proteins, easily progressing to end-stage liver diseases. Tao-Hong-Si-Wu-Tang (THSWT) is a traditional Chinese medicine formula applied in clinics to treat gynecological and chronic liver diseases. However, the role of THSWT on thioacetamide (TAA)-induced hepatic fibrosis and the specific mechanisms remains unclear. AIM OF THE STUDY: To investigate the improving effects of THSWT on TAA-insulted hepatic fibrosis and the underlying mechanisms. MATERIALS AND METHODS: UHPLC-MS/MS was performed to explore the chemical characterization of THSWT. Mice were orally administered with THSWT once daily for 6 weeks along with TAA challenge. Liver function was reflected through serum biomarkers and histopathological staining. RNA sequencing, non-targeted metabolomics and molecular biology experiments were applied to investigate the underlying mechanisms. RESULTS: THSWT profoundly repaired lipid metabolism dysfunction and blocked collagen accumulation both in TAA-stimulated mice and in hepatocytes. Results of RNA sequencing and non-targeted metabolomics revealed that the anti-fibrotic effects of THSWT mostly relied on lipid metabolism repairment by increasing levels of acetyl-CoA, phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine and lysophosphatidylethanolamine, and decreasing relative abundances of acyl-CoA, total cholesterol, diacylglycerol, triacylglycerol and phosphatidylinositol. Mechanically, long-chain acyl-CoA synthetases 4 (ACSL4) was a key profibrotic target both in human and mice by disrupting lipid oxidation and metabolism in hepatic mitochondria. THSWT effectively blocked ACSL4 and promoted mitophagy to reverse above outcomes, which was verified by mitophagy depletion. CONCLUSION: THSWT may be a promising therapeutic option for treating hepatic fibrosis and its complications by modulating lipid metabolism and promoting mitophagy in livers.

Effect of tao-hong-si-wu-tang, a traditional Chinese herbal medicine formula, on physical fatigue in mice.

Tao-Hong-Si-Wu-Tang (THSWT) is a famous traditional Chinese herbal medicine formula, which has traditionally been used in China for about one thousand years. The present study investigated the effect of THSWT on physical fatigue. 32 male mice were randomly divided into 4 groups with 8 in each group. All were administered orally and daily for 28 days. Group I received isotonic saline solution as control; Group II, III and IV obtained 5, 10 and 20ml/ kg body weight of THSWT solutions, respectively. After 28 days, the anti-physical fatigue effect of THSWT was evaluated by using a forced swimming test, along with the determination of blood lactic acid, blood urea nitrogen (BUN), liver glycogen and muscle glycogen contents. The data showed that THSWT could extend exhaustive swimming time of mice, as well as decrease the BLA and BUN contents and increase the liver glycogen and muscle glycogen contents. The results support that THSWT had anti-physical fatigue effect.