Atherosclerosis (AS) is the primary cause of cardiocerebrovascular disease, and inflammation is responsible for the initiation of its pathogenesis. Therefore, targeting inflammatory pathways to prevent AS progression is an ideal strategy. Angong Niuhuang pill (ANP) is a well-known traditional Chinese medicine and has been widely used for thousands of years to treat central nervous system and cardiovascular diseases. In this study, we investigated the role of ANP in reducing inflammation during early AS, using a high-fat diet-induced ApoE-/- mouse model of AS. Compared to those with simvastatin, ANP had no significant effect on serum triglyceride, low-density lipoprotein, and high-density lipoprotein levels. However, it effectively inhibited splenic and vascular inflammation. This agent also reduced the Th17/CD4+T ratio and mRNA expression of IL-6 and increased the Treg/CD4+T ratio and mRNA expression of TGF-β1. Thus, ANP restored Th17/Treg homeostasis in the spleen. It also regulated pro- and anti-inflammatory cytokine expression in the aorta in a similar manner. Further, it downregulated the expression of chemokine receptors (CCR2, CXCR3), their ligands (MCP-1, MCP-2, and MCP-3), and cell adhesion molecules (VCAM-1, ICAM-1) in arterial vessels. These results indicate that ANP can ameliorate the development of early AS, mainly by reducing inflammation instead of acting as an antihyperlipidemic drug.

Lung cancer is the most common cause of cancer death with high morbidity and mortality, which non-small-cell lung cancer (NSCLC) accounting for the majority. Traditional Chinese Medicine (TCM) is effective in the treatment of complex diseases, especially cancer. However, TCM is still in the conceptual stage. The interaction between different components remains unknown due to its multicomponent and multitarget characteristics. In this study, compound Liuju formula was taken as an example to isolate compounds with synergistic biological activity through systems pharmacology strategy. Through pharmacokinetic evaluation, 37 potentially active compounds were screened out. Meanwhile, 116 targets of these compounds were obtained by combing with the target prediction model. Through network analysis, we found that multicomponent drugs can present a synergistic effect through regulating inflammatory signaling pathway, invasion pathway, proliferation, and apoptosis pathway. Finally, it was confirmed that the bioactive compounds of compound Liuju formula have not only a killing effect on NSCLC tumor cells but also a synergistic effect on inhibiting the secretion of correlative inflammatory mediators, including TNF-α and IL-1β. The systems pharmacology method was applied in this study, which provides a new direction for analyzing the mechanism of TCM.

Rannasangpei (RSNP) is used as a therapeutic agent in the treatment of cardiovascular diseases, neurological disorders, and neurodegeneration in China; however, its potential use in the treatment of vascular dementia (VD) was unclear. In this study, our aim was to examine the neuroprotective effect of RSNP in a VD rat model, which was induced by permanent bilateral common carotid artery occlusion (2VO). Four-week administration with two doses of RSNP was investigated in our study. Severe cognitive deficit in the VD model, which was confirmed in Morris water maze (MWM) test, was significantly restored by the administration of RSNP. ELISA revealed that the treatments with both doses of RSNP could reinstate the cholinergic activity in the VD animals by elevating the production of choline acetyltransferase (ChAT) and reducing the acetylcholinesterase (AChE); the treatment of RSNP could also reboot the level of superoxide dismutase (SOD) and decrease malondialdehyde (MDA). Moreover, Western blot and quantitative PCR (Q-PCR) results indicated that the RSNP could suppress the apoptosis in the hippocampus of the VD animals by increasing the expression ratio of B-cell lymphoma-2 (Bcl-2) to Bcl-2-associated X protein (Bax). These results suggested that RSNP might be a therapeutic agent in the treatment of vascular dementia in the future.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome (MetS). The aim of the study was to evaluate the effects of Chinese herbal extracts from Salvia miltiorrhiza and Gardenia jasminoides (SGE) on the combination of NAFLD and MetS induced by a high-fat diet (HFD) in rats. After 6 weeks of HFD feeding, rats (n = 10 each group) were treated with saline, rosiglitazone (RSG), and SGE for 4 weeks. HFD rats were obese, hyperinsulinemic, hyperlipidemic and increased hepatic enzymes with the histological images of NAFLD. Treatment with SGE significantly reduced serum triglycerides (TG), nonesterified fatty acids and enhanced insulin sensitivity, and ameliorated the elevated serum hepatic enzymes compared with HFD-saline group. SGE treatment also attenuated hepatic TG by 18.5% (P < 0.05). Histological stains showed SGE decreased lipids droplets in hepatocytes (P < 0.05) and normalized macrovesicular steatosis in HFD rats. Significant reduction of TNF- α and IL6 in adipose tissue was detected in SGE treated rats. The anti-inflammatory action may be, at least in part, the mechanism of SGE on MetS associated with NAFLD. This study discovered that SGE is capable of managing metabolic and histological abnormalities of NAFLD and MetS. SGE may be an optimal treatment for the combination of NAFLD and MetS.

Infertility affects approximately 15% of couples around the world, and male factors are accounted for 40-50%. Oligoasthenozoospermia is the most common reason for male infertility. Unfortunately, effective drug therapy is still lacking except for assisted reproductive technology (ART). Previous researchers found that Wuzi Ershen decoction (WZESD) can increase sperm count, enhance sperm vitality, and improve semen quality. However, the pharmacological mechanisms remain unclear.

Holistic medicine is an interdisciplinary field of study that integrates all types of biological information (protein, small molecules, tissues, organs, external environmental signals, etc.) to lead to predictive and actionable models for health care and disease treatment. Despite the global and integrative character of this discipline, a comprehensive picture of holistic medicine for the treatment of complex diseases is still lacking. In this study, we develop a novel systems pharmacology approach to dissect holistic medicine in treating cardiocerebrovascular diseases (CCDs) by TCM (traditional Chinese medicine). Firstly, by applying the TCM active ingredients screened out by a systems-ADME process, we explored and experimentalized the signed drug-target interactions for revealing the pharmacological actions of drugs at a molecule level. Then, at a/an tissue/organ level, the drug therapeutic mechanisms were further investigated by a target-organ location method. Finally, a translational integrating pathway approach was applied to extract the diseases-therapeutic modules for understanding the complex disease and its therapy at systems level. For the first time, the feature of the drug-target-pathway-organ-cooperations for treatment of multiple organ diseases in holistic medicine was revealed, facilitating the development of novel treatment paradigm for complex diseases in the future.

Cisplatin (CDDP) is a potent antitumor compound widely used with a notably side effect of nephrotoxicity inducing oxidative stress and apoptosis in kidneys. Standardized extract from the leaves of the Ginkgo biloba trees, labeled EGb761 (EGb), has been available on the market for its beneficial effects. The purpose of this study was to investigate the ability of EGb to prevent the nephrotoxic effect of CDDP and the mechanisms involved. Our results showed that EGb treatment restored the levels of creatinine, BUN, MDA, NO, SOD, CAT, GPx, and GSSG/GSH ratio in kidneys after CDDP injection. EGb also exhibited a tendency to decrease the elevated NF- κ B translocation and caspase-3 protein levels in CDDP-treated kidneys. We further used a porcine kidney proximal tubular epithelial (LLC-PK1) cell line, finding that EGb accordingly inhibited ROS accumulation and iNOS increase induced by CDDP in vitro. EGb also attenuated I κ B degradation and p65 NF- κ B phosphorylation triggered by CDDP in LLC-PK1 cells. But EGb failed to influence CDDP-stimulated caspase cascade. These findings suggested that EGb's renoprotective effect might be mediated by not only its well-known antioxidant activity but also the anti-inflammatory activity.

Male C57BL/6J mice were used to establish AECOPD model by cigarette smoke and bacterial exposure. Mice were randomly divided into normal control (NC), AECOPD, XQLD, Compound C (Com C), Com C + XQLD, and Clarithromycin (CLA) groups. After treatment, the pulmonary function was evaluated by whole-body plethysmograph. The lung histopathology was observed by HE staining. The serum levels of IL-6, TNF-α, and COX-2 were detected by ELISA assay. The apoptotic index was measured by TUNEL assay, and the protein expressions of Bax, Bcl-2, Caspase-3, GRP78, and CHOP in the lung tissues were measured by western blot assay.

Guizhi Fuling capsule (GZFLc) is a modern preparation from traditional Chinese Medicine. Guizhi Fuling was first prescribed by Zhang Zhongjing almost two thousand years ago for the treatment of primary dysmenorrhea. It has also been used to treat uterine fibroids, dysfunctional uterine bleeding, and endometriosis. Although effective against dysmenorrhea clinically, there are limited information on the mechanism of its action. The major components responsible for the activity are not well defined. The aim of this study has been to elucidate a mechanism that may facilitate the development of a bioactivity-based assay for quality control during drug formulation and manufacturing. Using an oxytocin-induced mouse dysmenorrhea model, we showed that oral administration of GZFLc at 150 and 300 mg/kg, dosages relevant to clinic usages, significantly suppressed oxytocin-induced writhing response. The antidysmenorrhea effect was also demonstrated by a rotarod assay. We showed that GZFLc treatment significantly prolonged the hanging time of mice on the rotating rod. Histological studies showed that GZFLc treatment reduced lamina propria edema, while no effect on COX2 expression was detected. GZFLc instead exhibited direct inhibitory effect against COX2, a critical enzyme that catalyzes arachidonic acid conversion to prostaglandins. By HPLC profiling, we showed that paeoniflorin, paeonol, and cinnamaldehyde are the major components from the corresponding plants. At 5 and 10 mg/kg, both paeoniflorin and paeonol were active against induced dysmenorrhea. The study not only links GZFLc antidysmenorrhea activity to COX2 inhibition but also uncovers a mechanism of action by which an assay can be developed for bioefficacy evaluation of GZFLc.