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Xihuang pill has been utilized to treat cancer for more than three hundred years in China. The molecular mechanisms of Xihuang pill in treating glioblastoma remains unclear. This study aimed to explore the core molecular mechanisms of Xihuang pill in treating glioblastoma by an integrative pharmacology-based investigation. The main active compounds of Xihuang pill were identified from TCMSP, BATMAN-TCM, TCMID and CNKI. Glioblastoma-related therapeutic targets were retrieved from GeneCards and UniProt. Subsequently, a protein-protein interaction (PPI) network analysis was constructed using STRING. GO and KEGG enrichment were performed to analyze the intersection targets between the active compounds of Xihuang pill and glioblastoma. Based on the above analysis, we built a CTP network. The in vitro and in vivo experiments were further performed to validate the crucial molecular targets of Xihuang pill for the treatment of glioblastoma. A total of sixty active compounds of Xihuang pill and ten potential targets related to glioblastoma were found. Based on topological analysis, fourteen ingredients were selected as the main active compounds, and MY11 might be the most important metabolite in Xihuang pill. PI3K/Akt signaling pathway and receptor tyrosine kinases were considered as crucial targets for Xihuang pill against glioblastoma through KEGG enrichment and CTP analysis. The present experiments indicated that Xihuang pill suppressed the activation of PI3K/Akt/mTOR signaling pathway in glioblastoma cells and mouse xenografts via modulating the expression of PTEN and Rheb proteins, the interaction between TSC2 and Rheb, and the production of PIP3. Meanwhile, after glioblastoma cells treatment with Xihuang pil, the release of IL-1β, INF-γ was increased and the production of IL-10, TGF-β1 was decreased in glioblastoma cells after incubated with Xihuang pill. In addition, the activation of the upstream positive modulators of PI3K/Akt/mTOR pathway including PDGF/PDGFR and FGF/FGFR signaling were down-regulated in glioblastoma cells and mouse xenografts after treatment with Xihuang pill. Taken together, Xihuang pill inhibiting glioblastoma cell growth might be partly through down-regulating the activation of PDGF/PDGFR or FGF/FGFR-PI3K/Akt/mTOR signaling axis and improving immuno-suppressive micro-environment of glioblastoma. [Display omitted] • Glioblastoma with activated RTKs-PI3K/Akt/mTOR signaling has poor prognosis. • Xihuang pill (XHP) has been used for cancer treatment in China since 18th century. • XHP inhibits the activation of PDGF/PDGFR and FGF/FGFR signaling in glioblastoma. • XHP regulates PTEN expression, TSC2-Rheb interaction and PIP3 release in glioblastoma. • XHP induces IL-1β, INF-γ release and reduces IL-10, TGF-β1 production in glioblastoma. [ABSTRACT FROM AUTHOR]

A widely used traditional prescription, Yi-Gan San (YGS) is a remedy for neurodegenerative disorders. The formulation consists of seven Chinese medicinal materials in specific proportions, namely Uncariae Ramulus cum Uncis (Uncaria rhynchophylla (Miq.) Miq. ex Havil.), Bupleuri Radix (Bupleurum chinense DC.), Angelicae Sinensis Radix (Angelica sinensis (Oliv.) Diels), Chuanxiong Rhizoma (Ligusticum wallichii Franch.), Poria (Poria cocos (Schw.) Wolf), Atractylodis Macrocephalae Rhizoma (Atractylodes macrocephala Koidz.) and Glycyrrhizae Radix et Rhizoma (Glycyrrhiza uralensis Fisch.). Using YGS has been shown to alleviate various behavioural and psychological symptoms of dementia (BPSD). The goal of this review is to give up-to-date information about the traditional uses, chemistry, pharmacology and clinical efficacy of YGS based on the scientific literature and to learn the current focus and provide references in the next step. The database search room was accessed using the search terms "Yi-Gan San" and "Yokukansan" to obtain results from resources such as Web of Science, PubMed, Google Scholar and Sci Finder Scholar. We not only consulted the literature of fellow authors for this review but also explored classical medical books. YGS has been used to cure neurosis, sleeplessness, night weeping and restlessness in infants. Its chemical components primarily consist of triterpenes, flavonoids, phenolics, lactones, alkaloids and other types of compounds. These active ingredients displayed diverse pharmacological activities to ameliorate BPSD by regulating serotonergic, glutamatergic, cholinergic, dopaminergic, adrenergic, and GABAergic neurotransmission. In addition, YGS showed neuroprotective, antistress, and anti-inflammatory effects. The majority of cases of neurodegenerative disorders are treated with YGS, including Alzheimer's disease and dementia with Lewy bodies. Based on previous studies, YGS has been used as a traditional prescription in East Asia, such as Japan, Korea and China, and it has diverse chemical compounds and multiple pharmacological activities. Nevertheless, few experimental studies have focused on chemical and quantitative YGS studies, suggesting that further comprehensive research on its chemicals and quality assessments is critical for future evaluations of drug efficacy. [Display omitted] • Traditional uses, chemical compounds, pharmacological activities and clinical studies of Yi-Gan San (YGS) were concluded. • The research status about the traditional uses of YGS was presented in this review. • All know chemical constituents isolated from YGS and their chemical structures were proposed in this review. • The research on pharmacological effects and underlying mechanisms of YGS were summarized. • The clinical curative effects of YGS were outlined in detail. [ABSTRACT FROM AUTHOR]

Xiaojin Pills is a classic prescription for the treatment of mammary glands hyperplasia with a history of nearly 300 years, and is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinic. Clinical and animal studies have shown that Xiaojin Pills has the effects of anti-mammary glands hyperplasia, promoting blood circulation, anti-inflammation and analgesia. However, its initial administration method was "taking orally after soaked with Chinese Baijiu", the modern method was changed to "taking orally with water" in recent 20 years. Whether there is any difference in the efficacy of the two administration methods is still unknown. To reveal the difference in efficacy and metabolic mechanism of anti-mammary gland hyperplasia between the oral administration of Xiaojin Pills accompanied with Chinese Baijiu (XJP&B) and water (XJP&W). COX-2 inhibition rate test and anti-platelet aggregation activity test were used to investigate the efficacy difference between the 40 vol% Chinese Baijiu and water extracts of Xiaojin Pills on anti-inflammatory and blood-activating in vitro. Kunming male mice (20 ± 5 g) and SD female rats (200–220 g) were orally treated with XJP&B and XJP&W, respectively. Then the difference in anti-inflammatory and analgesic effects between XJP&B and XJP&W were evaluated via xylene-induced ear swelling test, formaldehyde-induced pain test, and acetic acid-induced writhing test in mice. Determination of nipple diameter, pathological examination of mammary gland tissue, determination of serum E 2 , P and FSH content and hemorheological parameters of rats with mammary gland hyperplasia were performed to explore the efficacy difference in anti-mammary gland hyperplasia between XJP&B and XJP&W. Metabolomics was used to study the difference of anti-mammary gland hyperplasia mechanism between XJP&B and XJP&W. The results showed that the effect of XJP&B was superior to that of XJP&W in anti-platelet aggregation, inhibition of inflammation and pain, and anti-mammary gland hyperplasia. Interestingly, the advantages were more significant under low-dose condition. In addition, the mechanism of the two combinations against mammary gland hyperplasia was indeed different. Their common metabolic pathways include tryptophan metabolism and alanine, aspartic acid and glutamic acid metabolism. However, Chinese Baijiu and XJP&B also have additional regulatory effects on linoleic acid metabolic pathway. In brief, this research demonstrated that the efficacy of XJP&B was better than that of XJP&W in activating the blood, anti-inflammation, analgesia and anti-mammary gland hyperplasia, which means that XJP&B has synergistic and superior effects. The special dose-effect relationship under the condition of XJP&B was also found, laying the foundation for clinical treatment to reduce the dosage and shorten the medication cycle, which is beneficial to reduce the economic burden of patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) play an important role in tumor metastasis and may be a target for metastasis prevention. The traditional Chinese medicine Jinfukang functions to improve immunity, prevent metastasis, and prolong lung cancer patient survival periods. Yet, whether Jinfukang prevents metastasis by regulating immune cells to clearance CTCs is still unknown. To explore the anti-metastasis mechanism of Jinfukang from the perspective of regulating NK cells to clear CTCs. CTC-TJH-01 cell was treated with Jinfukang. Cytokine chip was used to detect cytokines in cell culture supernatant. Lymphocyte recruitment assay was detected by Transwell and flow cytometry. Protein expression was analysis by Western blot. LDH kit was used to detect cytotoxicity. NOD-SCID mice used for tail vein injection to study lung metastasis. Jinfukang could promote the expression and secretion of the chemokine CX3CL1 by CTCs. In addition, Jinfukang could promote the recruitment of natural killer (NK) cells by CTCs and significantly increase the cytotoxic effect of NK cells on CTCs. Moreover, Jinfukang could upregulate the expression of FasL and promote the secretion of TNF-α by NK cells and that NK cells could induce the apoptosis of CTCs through the Fas/FasL signaling pathway. Finally, we confirmed that Jinfukang could promote NK cells to kill CTCs and then inhibit lung cancer metastasis in vivo. The above effects of Jinfukang could be partially reversed by an anti-CX3CL1 mAb. These results suggest that Jinfukang may prevent lung cancer metastasis by enhancing the clearance of CTCs in the peripheral blood by NK cells, providing evidence for the anti-metastasis effect of Jinfukang. [Display omitted] [ABSTRACT FROM AUTHOR]

Tripterygium wilfordii Hook F. (TwHF), a traditional Chinese herb medicine, has been widely used for clinical treatment of various rheumatic immune diseases. Tripterygium glycosides (TG) extracted from TwHF has been verified to process multiple bioactivities, including immunosuppressive, anti-inflammatory and anti-cancer effects. However, the clinical application of TG is limited due to its severe toxicity and narrow therapeutic window. For the clinical safety of TG usage, attenuation of toxicity is the key issue to be solved. Tripterygium glycoside fraction n2 (TG-n2) is a detoxified mixture obtained from TG using a new preparation method. In our previous study, we have demonstrated that TG-n2 has a lower toxicity than TG. The aim of the present study was to screen the renal protective effect of TG-n2 in nephrotic syndrome (NS) induced by adriamycin (ADR) in rats and its effect on apoptosis, as well as the effective difference between TG-n2 and TG. The ADR-induced NS rat model was established. Rats were intravenously injected with ADR (6 mg/kg), then treated with either TG-n2 (10 mg/kg/day) or TG (10 mg/kg/day) by oral gavage for 4 weeks. Clinical indexes in each group were determined. HE staining and electron microscopic analysis were used to evaluate renal histopathological damage. Caspase-3 activity reagent and TUNEL staining were used to estimate renal apoptosis. Protein levels of caspase-3, caspase-9, caspase-8, caspase-12, Bax, Bcl-2, p53, TNF-R1, FLIP and podocin were measured by Western Blot. TG-n2 and TG intervention ameliorated renal function as assessed by the levels of 24-h proteinuria, Cr, BUN, TC, TG, ALB and LDL-c. TG-n2 and TG alleviated the decrease of podocin protein expression and morphological injury of podocyte as screened by Western Blot and electron microscopic analysis. Besides, renal tubular injury was reduced as inspected by light microscopic analysis. TG-n2 and TG could significantly inhibit the apoptosis and activity of caspase-3 in kidney tissues as examined by fluorescence microscopic analysis and reagent. After intervention of TG-n2 and TG, protein levels of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, Bax, p53 and TNF-R1 in renal issues were significantly decreased compared with ADR group. In contrast, protein level of Bcl-2 was elevated remarkedly. Our data suggested that attenuated TG-n2 may have a similar protective effect with TG in ADR-induced NS in rats by inhibiting activation of apoptosis. Image 1 • First report on protective effect of Tripterygium glycoside fraction n2 in adriamycin-induced nephrotic syndrome in rats. • Apoptosis was adaptively reduced by treatment of Tripterygium glycoside fraction n2. • Tripterygium glycoside fraction n2 shares similar curative effect of nephrotic syndrome with Tripterygium glycosides. [ABSTRACT FROM AUTHOR]