ShaShen-MaiDong decoction attenuates bleomycin-induced pulmonary fibrosis by inhibiting TGF-ß/smad3, AKT/MAPK, and YAP/TAZ pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary fibrosis (PF) is progressive and terminal lung disease, which is also the most common sequelae of Corona Virus Disease (2019) (COVID-19) survivors. Unfortunately, there is currently no cure for PF. ShaShen-MaiDong decoction (SMT), a traditional Chinese medicine, has been employed in treating various lung diseases, which may offer potential therapeutic benefits for PF. AIM OF THE STUDY: To investigate the antifibrotic efficacy of SMT and its major active ingredients as well as the underlying mechanisms for treating PF. MATERIALS AND METHODS: Fist, we build the UPLC-MS based qualitative and quantitative profiling for the quality control of SMT. Then, the antifibrotic efficacy of SMT was investigated in bleomycin (BLM)-induced PF mice model. Network pharmacology was used to predict the mechanism and active components of SMT for the treatment of PF, which was further verified in vitro and in vivo. RESULTS: SMT improved the weight loss and attenuated hydroxyproline, inflammatory cytokines, and collagen deposition in BLM-induced PF mice model in a dose-dependent manner. Mechanistically, as predicted by network pharmacology analysis, SMT and its active compounds (kaempferol, quercetin, and isorhamnetin) regulated the mitogen-activated protein kinase (MAPK) signaling pathways, TGF-ß/Smad signaling pathway, and YAP/TAZ signaling pathway, which was further verified in the PF mice and TGF-ß-induced A549 cell model. Moreover, SMT balanced the proportions of increased CD4+ and decreased CD8+ T cells in the peripheral blood of PF mice model. CONCLUSIONS: Considering the high mortality and complex pathogenesis of fibrotic diseases, our results provide novel evidence that SMT would be beneficial for pulmonary fibrosis therapy by modulating MAPK, TGF-ß/Smad, and YAP/TAZ signaling pathways at same time.

The Efficacy and Safety of Shashen-Maidong Decoction Combined with Western Medicine in the Treatment of Omicron Infected Individuals Over 85 Years Old: A Retrospective Study.

Background: During the Omicron variant outbreak of COVID-19 (2022-2023), Chinese healthcare institutions combined traditional Chinese medicine (TCM) with Western medical practices to treat COVID-19 patients, especially the elderly. The efficacy and safety of this approach, especially for individuals aged over 85, need further investigation. Methods: In this retrospective study, a cohort of 62 patients aged over 85 years, diagnosed with COVID-19 infection, was examined. Among them, 34 patients were administered Shashen-Maidong decoction in conjunction with Western medicine (SMD+WM group), while the remaining 28 patients received only Western medicine (WM group). Comparative analysis was conducted between the two groups, encompassing parameters such as the duration for the nucleic acid test to turn negative, length of intensive care unit (ICU) stay, mortality rate, utilization of high-flow nasal cannula oxygen (HFNC), occurrence of endo-tracheal intubation, frequency of recurrent respiratory infections within three months, and various laboratory indicators. Results: There were no significant differences observed between the two groups in terms of the duration for the nucleic acid test to turn negative, the length of ICU stay, mortality rate, utilization of HFNC, performance of endo-tracheal intubation, or the frequency of recurrent respiratory infections within three months (P > 0.05). However, in comparison to the WM group, the SMD+WM group exhibited notably lower growth rates in white blood cell (WBC) and neutrophil (NEUT) values. Additionally, the SMD+WM group demonstrated superior improvement in cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP) values. Conclusion: In contrast to the administration of Western medicine alone, the combined use of Shashen-Maidong decoction with Western medicine significantly suppresses the increase in WBC count, particularly in NEUT levels, in elderly patients diagnosed with COVID-19. Moreover, this combined treatment exhibits a protective effect on cardiac function and demonstrates a relatively safe profile.

Decoding the key compounds and mechanism of Shashen Maidong decoction in the treatment of lung cancer.

BACKGROUND: Lung cancer is a malignant tumour with the fastest increase in morbidity and mortality around the world. The clinical treatments available have significant side effects, thus it is desirable to identify alternative modalities to treat lung cancer. Shashen Maidong decoction (SMD) is a commonly used traditional Chinese medicine (TCM) formula for treating lung cancer in the clinic. While the key functional components (KFC) and the underlying mechanisms of SMD treating lung cancer are still unclear. METHODS: We propose a new integrated pharmacology model, which combines a novel node-importance calculation method and the contribution decision rate (CDR) model, to identify the KFC of SMD and to deduce their mechanisms in the treatment of lung cancer. RESULTS: The enriched effective Gene Ontology (GO) terms selected from our proposed node importance detection method could cover 97.66% of enriched GO terms of reference targets. After calculating CDR of active components in key functional network, the first 82 components covered 90.25% of the network information, which were defined as KFC. 82 KFC were subjected to functional analysis and experimental validation. 5-40 µM protocatechuic acid, 100-400 µM paeonol or caffeic acid exerted significant inhibitory activity on the proliferation of A549 cells. The results show that KFC play an important therapeutic role in the treatment of lung cancer by targeting Ras, AKT, IKK, Raf1, MEK, and NF-κB in the PI3K-Akt, MAPK, SCLC, and NSCLC signaling pathways active in lung cancer. CONCLUSIONS: This study provides a methodological reference for the optimization and secondary development of TCM formulas. The strategy proposed in this study can be used to identify key compounds in the complex network and provides an operable test range for subsequent experimental verification, which greatly reduces the experimental workload.

Shashen-Maidong Decoction inhibited cancer growth under intermittent hypoxia conditions by suppressing oxidative stress and inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Lung cancer is one of the most common malignant tumours and has become the leading cause of cancer-related deaths worldwide. Abnormal microcirculation during tumour growth leads to intermittent hypoxia (IH), which is responsible for promoting cancer cell proliferation and migration. Patients with advanced lung cancers show deficiency of both Qi and Yin Syndrome (DQYS) in TCM, and studies have confirmed that IH exposure is related to DQYS. Shashen-Maidong Decoction (SMD), has been widely applied clinically targeting DQYS and has a long history for treating lung cancer by nourishing the body's "zheng qi" and resisting "xie qi". However, whether SMD could be beneficial to lung cancer under IH conditions remains unclear. AIM OF THE STUDY: This study aimed to clarify the effects and mechanism of SMD on non-small cell lung cancer (NSCLC) growth under IH conditions. MATERIALS AND METHODS: C57 mice were injected subcutaneously into the right axilla with Lewis lung cancer (LLC) cells and exposed to IH conditions (21%-5% O2, 5 min/cycle, 8 h/day) for 21 days. SMDs were orally treated with different concentrations (2.6, 5.2 or 10.4 g/kg/day) 30 min before IH exposure. Tumour proliferation and migration were assessed by HE and IHC staining, and oxidative stress was assessed by DHE staining and MDA or SOD detection. IL-6, IL-1ß and TNF-α levels were assessed by IHC staining, and the IL-6/JAK2/STAT3 signalling pathway was detected by western blotting. RESULTS: Our results showed that SMD treatment inhibited tumour growth and liver metastasis in LLC-bearing mice exposed to IH, decreased Ki67, CD31, VEGF, and MMP-2, and increased E-cadherin expression in tumourt tissue. SMD reduced ROS production, increased SOD levels and SOD-2 expression, and decreased MDA levels and NOX-2 expression. SMD decreased IL-6, IL-1ß and TNF-α levels, reduced IL-6 expression and inhibited JAK2 and STAT3 phosphorylation. Additionally, SMD treatment improved DQYS and liver and kidney function in LLC-bearing mice under IH conditions. CONCLUSION: Our research suggests that SMD treatment can inhibit tumour growth in mice exposed to IH. The antitumour effect of SMD may be related to attenuated oxidative stress and inflammation through inactivation of the IL-6/JAK2/STAT3 signalling pathway under IH conditions.

Clinical Efficacy and Safety of Shashen Maidong Decoction in the Treatment of Pediatric Mycoplasma Pneumonia: A Systematic Review and Meta-Analysis.

Objective: This study was intended to provide data to support the effect of Shashen Maidong Decoction in improving mycoplasma pneumonia in pediatric patients through systematic evaluation. Methods: PubMed, the Web of Science, EMbase, CNKI, CQVIP, Wan-Fang, and CBM databases were comprehensively searched from established in June 2021. Randomized controlled trials of TRQI were selected by screening the literature and extracting information. The Cochrane RCT Evaluation Manual was used to evaluate the methodological quality of all included studies, and Meta-analysis was performed using Stata 14.0 and Review Manager 5.4 software. Results: A total of 1,127 patients from 12 clinical studies met the inclusion criteria. Meta-analysis results showed that the treatment group of Shashen Maidong Decoction was able to significantly increase the overall efficiency level and significantly reduce the incidence of adverse reactions, time for disappearance of cough, time for relief of cough, time for defervescence, time for disappearance of lung rales, time for return to normal of chest X-ray, T lymphocyte subpopulation (CD3+) and tumor necrosis factor-α (TNF-α) and other index levels (p < 0.05). Conclusion: Shashen Maidong Decoction has a significant improvement in the levels of relevant indexes in pediatric mycoplasma pneumonia, which provides a basis for the safety and efficacy of pediatric mycoplasma pneumonia. However, due to the small sample size included in the study, the study quality was not high, and more randomized controlled trials of high quality are required for further validation.

Shashen maidong decoction: the effect of TNF-α and IL-6 on lung cancer cachexia based on cancer toxicity theory.

OBJECTIVE: To study the curative effect of the traditional Chinese medicine (TCM) Shashen Maidong Decoction in treating lung cancer cachexia based on the cancer toxicity theory, and analyze its influence on patients' serum tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). METHODS: From January 2018 to January 2019, 104 patients with primary lung cancer cachexia diagnosed and treated in our hospital's oncology department were selected and randomly divided into experimental group and control group, with 52 cases in each group. The control group received routine treatment and nutritional support, while the experimental group received Shashen Maidong Decoction plus. Indexes were compared and analyzed before and after 4 weeks of treatment, including TCM syndrome score, Patient-Generated Subjective Global Assessment (PG-SGA) score, Karnofsky score (KPS), albumin, prealbumin, TNF-α and IL-6 levels. RESULTS: (1) After treatment, both groups' PG-SGA score, KPS score and TCM syndrome score were better than those before treatment (P < 0.01), and the experimental group's PG-SGA score, KPS score and TCM syndrome score were higher than those of the control group (P < 0.01). (2) After treatment, both groups' serum albumin and prealbumin levels were higher than those before treatment (P < 0.05), and the experimental group's prealbumin level was higher than that in the control group (P < 0.05). (3) After treatment, both groups' serum levels of TNF-α and IL-6 were lower than those before treatment (P < 0.05), and the experimental group's levels of TNF-α and IL-6 were lower than those in the control group (P < 0.05). CONCLUSION: Based on the cancer toxicity theory, the application of Shashen Maidong Decoction in treating lung cancer cachexia has definite therapeutic effects and important clinical values. It can effectively alleviate patients' symptoms, improve nutritional status, and reduce body's inflammatory response.