Integrating Network Pharmacology and Experimental Validation to Elucidate the Mechanism of Yiqi Yangyin Decoction in Suppressing Non-Small-Cell Lung Cancer.

Yiqi Yangyin Decoction (YYD) is a classic traditional Chinese medicine (TCM) formulation to treat lung cancer in clinic. Nevertheless, the active ingredients, key targets, and molecular mechanisms for YYD are still poorly understood. This study is focused on elucidating the pharmacological mechanism of YYD in non-small-cell lung cancer (NSCLC) by using a combined network pharmacology approach and biological experiment validation. Online bioinformatics tools showed that 40 bioactive compounds and 229 putative targets of YYD were associated with anti-NSCLC activity. Protein-Protein Interaction (PPI) network demonstrated AKT1, SRC, JUN, TP53, and EGFR as the top five key targets for YYD against NSCLC. Through enrichment analysis, YYD was found to affect cell proliferation and apoptosis in NSCLC possibly by PI3K-AKT signaling. Molecular docking confirmed a strong binding between the main compounds (quercetin or luteolin) and EGFR. As demonstrated by CCK-8, EdU, and colony formation assays, we found a significant inhibition of YYD on cell proliferation. Moreover, YYD treatment induced cell cycle arrest by affecting p53, p21, and cyclin D1 expression. YYD administration enhanced apoptosis by changing the expression of cleaved caspase-3, Bax, and Bcl-2. Mechanistically, YYD resulted in a significant inactivation of EGFR-PI3K-AKT signaling. Furthermore, EGFR activator significantly reversed YYD-mediated proliferation inhibition and apoptosis. YYD also showed an inhibitory effect on tumor growth in mice. Together, YYD might target the EGFR-PI3K-AKT pathway to repress NSCLC progression.

[Effects of Chinese herbal medicine Shenxiong Yujing Granule on regeneration of neural cells in rats with diabetes-associated cerebral ischemia].

OBJECTIVE: To establish a rat model of diabetes-associated cerebral ischemia due to qi and yin deficiency and blood stasis, and to investigate the effects of Radix Ginseng, Rhizoma Chuanxiong, Rhizoma Polygonati Odorati and Rhizoma Polygonati Sibirici Granule (Shenxiong Yujing Granule), which has the function of strengthening qi, nourishing yin, and activating blood, on proliferation, differentiation and survival of neural cells in rats with diabetes-associated cerebral ischemia. METHODS: Rats were divided into sham-operation, diabetes plus ischemia reperfusion injury model, Shenxiong Yujing Granule and Radix Ginseng and Rhizoma Chuanxiong Granule (Shenxiong Granule) groups with 20 rats in each. The 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and immunohistochemical method were used to investigate the proliferation, differentiation and survival of neural cells in dentate gyrus of rats with diabetes-associated cerebral ischemia. RESULTS: The number of newly proliferating cells in subgranular zone of dentate gyrus was increased in the model group, but there was no significant difference compared with 7 day treatment with Shenxiong Yujing Granule. Shenxiong Yujing Granule significantly increased the survival rate and promoted the differentiation of newly proliferating neurons after 21-day treatment (P<0.01). In addition, the beneficial effect of Shenxiong Yujing Granule was considerably greater than that of the Shenxiong Granule (P<0.01). CONCLUSION: Shenxiong Yujing Granule can increase the survival rate and promote the differentiation of newly proliferating neurons in rats with diabetes-associated cerebral ischemia of dual deficiency of qi and yin and blood stasis obstructing the collaterals. The effect is greater than that of Shenxiong Granule.

Electroacupuncture at ST-36 relieves visceral hypersensitivity and decreases 5-HT(3) receptor level in the colon in chronic visceral hypersensitivity rats.

PURPOSE: Visceral hypersensitivity is an important pathological mechanism of irritable bowel syndrome. Electroacupuncture (EA) could relieve chronic visceral hypersensitivity (CVH) in rats. However, little information is available about the mechanism. The aim of this study was to confirm the effects of EA at acupoint ST-36 (Zusanli) on CVH induced by the chemical colorectal irritation during postnatal development of rats, and to explore the possible 5-HT(3) receptor mechanism. METHODS: Rats were randomized into four groups, including the normal control group, CVH group, CVH with EA group, and CVH with sham EA group. The abdominal electromyogram (EMG) in response to colorectal distension was selected as the index for measurement of visceral hypersensitivity. 5-HT(3) receptors were analyzed through reverse transcription-polymerase chain reaction and western blot. RESULTS: EA at ST-36 significantly decreased evoked EMG. The expression of 5-HT(3) receptor in the colon was increased in rats with CVH, and decreased after EA treatment. CONCLUSIONS: EA at acupoint ST-36 attenuates CVH in rats and decreases 5-HT(3) receptor level in the colon. Decreased 5-HT(3) receptor level in the colon may mediate the beneficial effect of EA in rats with CVH.