Hovenianin A Alleviates Hepatic Fibrosis by Inhibiting the PI3K/AKT Pathway in TGF-ß1-Induced HSCs Based on Network Pharmacology and Transcriptomic Analysis.

Hepatic fibrosis is a global health problem, which currently has no FDA approved antifibrotic therapy yet. This study aimed to explore the mechanism of Hovenia genus in the treatment of hepatic fibrosis by an integrative strategy combining network pharmacology analysis, molecular docking, transcriptomics and experimental validation. The traditional Chinese medicine systems pharmacology (TCMSP) database and literatures were used to collect the components of Hovenia genus. Public databases including GeneCards, TTD, PharmGkb were used to acquire the putative targets. The GO and KEGG analysis were applied to explore the underlying mechanisms. Furthermore, The TGF-ß1 induced hepatic stellate cells (HSCs) model were performed to evaluate the anti-hepatic fibrosis activity of Hovenia genus. The RT-qPCR, Western blotting and flow cytometry experiments were used to validate the anti-hepatic fibrosis mechanisms of Hovenianin A. The KEGG analysis of network pharmacology and transcriptomics revealed that the core targets mainly enriched in PI3K-Akt signaling pathways. The cell screening results indicated flavonoids were the main active ingredients of Hovenia. Hovenianin A, a bioactive bisflavonol, was validated to promote the apoptosis of HSCs by inhibiting PI3K-Akt pathway. Molecular docking further corroborated the binding sites between Hovenianin A and AKT1. In summary, Hovenia may have therapeutic effects on liver fibrosis by modulating the PI3K-Akt apoptosis pathway. Our findings may facilitate the development of Hovenia genus, which could help to treat liver fibrosis in the future.

Ethyl cinnamate suppresses tumor growth through anti-angiogenesis by attenuating VEGFR2 signal pathway in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga Linn. is an aromatic medicinal herb with extensively applied in India, China, Malaysia and other South Asia countries for thousands of years. It has been mentioned to treat abdominal tumors. Ethyl cinnamate (EC), one of the main chemical constituents of the rhizome of K. galanga, exhibited nematocidal, sedative and vasorelaxant activities. However, its anti-angiogenic activity, and anti-tumor effect have not been investigated. AIM OF THE STUDY: To investigate the anti-angiogenic mechanism of EC and its anti-tumor effect by suppressing angiogenesis. MATERIALS AND METHODS: The in vitro anti-angiogenic effect was evaluated using HUVECs model induced by VEGF and zebrafish model in vivo. The influence of the EC on phosphorylation of VEGFR2 and its downstream signaling pathways were evaluated by western blotting assay. Molecule docking technology was conducted to explore the interaction between EC and VEGFR2. SPR assay was used for detecting the binding affinity between EC and VEGFR2. To further investigate the molecular mechanism of EC on anti-angiogenesis, VEGFR2 knockdown in HUVECs and examined the influence of the EC. Anti-tumor activity of EC was evaluated using colony formation assay and apoptosis assay. The inhibitory effect of EC on tumor growth was explored using HT29 colon cancer xenograft model. RESULTS: EC obviously inhibited proliferation, migration, invasion and tube formation of VEGF-induced HUVECs. EC also induced apoptosis of HUVECs. Moreover, it inhibited the development of vessel formation in zebrafish. Further investigations demonstrated that EC could suppress the phosphorylation of VEGFR2, and its downstream signaling pathways were altered in VEGF-induced HUVECs. EC formed a hydrogen bond to bind with the ATP binding site of the VEGFR2, and EC-VEGFR2 interaction was shown in SPR assay. The suppressive effect of EC on angiogenesis was abrogated after VEGFR2 knockdown in HUVECs. EC inhibited the colon cancer cells colony formation and induced apoptosis. In addition, EC suppressed tumor growth in colon cancer xenograft model, and no detectable hepatotoxicity and nephrotoxicity. In addition, it inhibited the phosphorylation of VEGFR2, and its downstream signal pathways in tumor. CONCLUSIONS: EC could inhibit tumor growth in colon cancer by suppressing angiogenesis via VEGFR2 signaling pathway, and suggested EC as a promising candidate for colon cancer treatment.

Integrating Network Pharmacology and Experimental Validation to Investigate the Mechanism of Qushi Huatan Decoction Against Coronary Heart Disease.

Purpose: This study was designed to evaluate the effect and mechanism of the Qushi Huatan (QSHT) decoction against coronary heart disease (CHD) through network pharmacology and experimental verification. Methods: In the present study, the active ingredients of the QSHT decoction were identified by ultra performance liquid chromatography/tandem mass spectrometry (UPLC/MS), then the potential ingredients and coronary heart disease targets were predicted using the SwissTarget Prediction database and the database of Genecards and OMIM database, respectively. A herb-compound-target network was constructed using Cytoscape. GO and KEGG enrichment analysis were performed using the ClusterProfiler data package of R software. Molecular docking was used to predict the core targets of QSHT against CHD. In addition, we used a myocardial infarction (MI) and high-fat diet ApoE-/- mice model to investigate the cardioprotective effects of QSHT. Western blotting and immunochemistry were used to verify the core targets and the signaling pathway. Results: A total of 68 active ingredients were found in the QSHT decoction. Network pharmacology indicated 28 targets and 147 signal pathways, including AKT1, HIF-1α, GSK-3ß, TLR4 and NF-κB, those key targets were also verified by molecular docking. The results of GO and KEGG enrichment analysis showed that the targets of QSHT against CHD were largely associated with inflammatory and oxidative stress, and AKT/HIF-1α and TLR4/NF-κB pathways might be key functional pathways. In vivo, QSHT significantly improved cardiac function and attenuated fibrosis and inflammation. Furthermore, QSHT could significantly inhibit the expression of HIF-1α, TLR4, phosphorylation of AKT1, GSK-3ß and NF-κB after MI in ApoE-/- mice. Conclusion: Based on network pharmacology, molecular docking and experimental verification, this study demonstrated that QSHT could improve cardiac function and attenuate cardiac fibrosis by regulating TLR4/NF-κB and AKT/HIF-1α signaling pathway in post- MI and high-fat diet ApoE-/- mice.

Traditional Uses, Phytochemistry, Pharmacology, Quality Control, Industrial Application, Pharmacokinetics and Network Pharmacology of Pogostemon cablin: A Comprehensive Review.

Pogostemonis Herba (PH) is the dried aerial parts of Pogostemon cablin (Blanco) Benth, which is mainly distributed and used in Asian countries. PH is an aromatic damp-resolving drug in traditional Chinese medicine (TCM), which is usually used for the treatment of vomiting, chest tension, tiredness, abdominal pain, diarrhea, and headache. In this review, the summary of chemical constituents in the aerial parts, biological activities, history of uses, quality control methods, industrial applications, pharmacokinetics and network pharmacology are reported. By collating the chemical constituents of various parts of PH, a total of 174 components were identified, including 66 terpenes, 6 pyrones, 40 flavonoids, 21 phenylpropanoids, 9 steroids, 4 polysaccharides and 28 others. Pharmacological research has found that PH possesses multi-pharmacological activities, including regulating the gastrointestinal tract, inhibition of pathogenic microorganisms, and anti-inflammation, which provide more scientific interpretation for the clinical usage of PH. In addition, the shortcomings of the current research on PH and the recommendation of future studies on PH are analyzed. We hope this review can provide some insight for further research and applications of PH in future.

The pharmacology, pharmacokinetics, and toxicity of spinosin: A mini review.

Spinosin, a natural flavone-C-glycoside that is mainly isolated from the seeds of Ziziphus jujuba Mill. var. spinosa. It exerts the effects to ameliorate the neurological disorders, such as hypnosis effects, improvement of cognitive function, sedation effects, and anxiolytic effects, as well as anti-melanogenic effect, cardioprotective effects, and anti-cancer activity. However, the insufficient basic research, unclear mechanisms, and poor bioavailability may limit the prospects of spinosin in clinical utilization. In this review, we comprehensively summarized the latest information on the pharmacology, pharmacokinetics, toxicity, and NMR characteristic of spinosin, to evaluate its potential therapeutic for clinical application, hoping to provide some rational perspective for the innovative agent development and usage of spinosin in future.

[Changes of bone mass after implantation of Bio-Oss bone powder combined with platelet-rich fibrin for guided bone regeneration in alveolar bone defects].

PURPOSE: To investigate the effect of Bio-Oss bone powder combined with platelet-rich fibrin on bone mass after implantation-guided bone regeneration in alveolar bone defects. METHODS: One hundred and six patients with single anterior tooth loss and labial alveolar bone defect were selected for implant implantation and guided bone regeneration at the same time. Patients in the experimental group (n=53) were treated with Bio-Oss bone powder combined with platelet-rich fibrin and biofilm to guide bone regeneration, while patients in the control group(n=53) were treated with Bio-Oss bone powder combined with biofilm to guide bone regeneration. The success rate of implantation, complication rate, the thickness of labial bone wall and the regeneration of bone defect were observed. Statistical analysis was performed on the data using SPSS 25.0 software package. RESULTS: There was no significant difference in the success rate of implants between the two groups(96.23% vs 88.68%, P>0.05). The thickness of the labial bone wall of the experimental group 12 months after implantation was significantly higher than that of the control group[(2.72±0.43) mm vs(2.51±0.36) mm], and the thickness of the labial wall of the implant at different sites was significantly greater than that of the control group(P<0.05). Bleeding index [(0.32±0.02) vs (0.42±0.03)], depth of probing [(3.31±0.69) mm vs (4.32±0.95) mm], loss of attachment [(3.06±0.52) mm vs (5.24±1.35) mm] was significantly smaller in the experimental group than in the control group (P<0.05); bone graft height [(2.61±0.52) mm vs (2.31±0.35) mm], osteogenesis height [(2.59±0.32) mm vs (2.01±0.16) mm] was significantly greater in the experimental group than in the control group(P<0.05). There was no significant difference in the incidence of complications between the two groups(1.89% vs 5.66%, P>0.05). CONCLUSIONS: Bio-Oss bone powder combined with platelet-rich fibrin can reduce bone loss and promote bone defect regeneration after guided bone regeneration.