Gypenosides exert cardioprotective effects by promoting mitophagy and activating PI3K/Akt/GSK-3ß/Mcl-1 signaling.

Background: Gynostemma pentaphyllum (Thunb.) Makino, a well-known edible and medicinal plant, has anti-aging properties and is used to treataging-associated conditions such as diabetes, metabolic syndrome, and cardiovascular diseases. Gypenosides (GYPs) are the primary constituents of G. pentaphyllum. Increasing evidence indicates that GYPs are effective at preserving mitochondrial homeostasis and preventing heart failure (HF). This study aimed to uncover the cardioprotective mechanisms of GYPs related to mitochondrial regulation. Methods: The bioactive components in GYPs and the potential targets in treating HF were obtained and screened using the network pharmacology approach, followed by drug-disease target prediction and enrichment analyses. The pharmacological effects of GYPs in cardioprotection, mitochondrial function, mitochondrial quality control, and underlying mechanisms were further investigated in Doxorubicin (Dox)-stimulated H9c2 cardiomyocytes. Results: A total of 88 bioactive compounds of GYPs and their respective 71 drug-disease targets were identified. The hub targets covered MAPK, EGFR, PI3KCA, and Mcl-1. Enrichment analysis revealed that the pathways primarily contained PI3K/Akt, MAPK, and FoxO signalings, as well as calcium regulation, protein phosphorylation, apoptosis, and mitophagy process. In Dox-stimulated H9c2 rat cardiomyocytes, pretreatment with GYPs increased cell viability, enhanced cellular ATP content, restored basal oxygen consumption rate (OCR), and improved mitochondrial membrane potential (MMP). Furthermore, GYPs improved PINK1/parkin-mediated mitophagy without influencing mitochondrial fission/fusion proteins and the autophagic LC3 levels. Mechanistically, the phosphorylation of PI3K, Akt, GSK-3ß, and the protein level of Mcl-1 was upregulated by GYP treatment. Conclusion: Our findings reveal that GYPs exert cardioprotective effects by rescuing the defective mitophagy, and PI3K/Akt/GSK-3ß/Mcl-1 signaling is potentially involved in this process.

Combined untargeted metabolomics and network pharmacology approaches to reveal the therapeutic role of withanolide B in psoriasis.

Psoriasis is a refractory inflammatory skin disorder in which keratinocyte hyperproliferation is a crucial pathogenic factor. Up to now, it is commonly acknowledged that psoriasis has a tight connection with metabolic disorders. Withanolides from Datura metel L. (DML) have been proved to possess anti-inflammatory and anti-proliferative properties in multiple diseases including psoriasis. Withanolide B (WB) is one of the abundant molecular components in DML. However, existing experimental studies regarding the potential effects and mechanisms of WB on psoriasis still remain lacking. Present study aimed to integrate network pharmacology and untargeted metabolomics strategies to investigate the therapeutic effects and mechanisms of WB on metabolic disorders in psoriasis. In our study, we observed that WB might effectively improve the symptoms of psoriasis and alleviate the epidermal hyperplasia in imiquimod (IMQ)-induced psoriasis-like mice. Both network pharmacology and untargeted metabolomics results suggested that arachidonic acid metabolism and arginine and proline metabolism pathways were linked to the treatment of psoriasis with WB. Meanwhile, we also found that WB may affect the expression of regulated enzymes 5-lipoxygenase (5-LOX), 12-LOX, ornithine decarboxylase 1 (ODC1) and arginase 1 (ARG1) in the arachidonic acid metabolism and arginine and proline metabolism pathways. In summary, this paper showed the potential metabolic mechanisms of WB against psoriasis and suggested that WB would have greater potential in psoriasis treatment.

Potential effects and mechanisms of Chinese herbal medicine in the treatment of psoriasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoriasis is a chronic inflammatory dermatosis related to high morbidity and mortality. The incidence of psoriasis is increasing in recent decades. Some patients with psoriasis are anxious about the underlying side effects of synthetic drugs they are on. Therefore, they are eager to seek alternative and efficient therapy, such as Chinese herbal medicine (CHM). Researchers have found some CHM provides best source for the development of anti-psoriatic drugs because of their structural diversity and fewer adverse reactions. Some of CHM formulas or active constituents extracted from CHM have been rapidly developed into clinical drugs with good efficacy. At present, along with the CHM formulas, single CHM and its active components have been extensively accepted and utilized in the treatment of psoriasis, whose therapeutic mechanisms hitherto have not been thoroughly illustrated. AIM OF THE STUDY: This review aimed to comprehensively summarize about the existing therapeutic mechanisms of CHM in the treatment of psoriasis and to provide a reference to develop future related studies in this field. MATERIALS AND METHODS: Relevant literatures about how CHM treated psoriasis were acquired from published scientific studies (including PubMed, CNKI, Web of Science, Baidu Scholar, The Plant List, Elsevier and SciFinder). All plants appearing in the review have been included in The Plant List or Medicinal Plant Names Services (MPNS). RESULTS: In this review, we collect numerous literatures about how CHM treats psoriasis via immune cells, signaling pathways and disease-related mediators and systematically elucidates potential mechanisms from the point of the suppression of oxidative stress, the inhibition of abnormal abnormal proliferation and differentiation, the inhibition of immune responses, and the suppression of angiogenesis. CONCLUSIONS: Psoriasis is considered as a complicated disease caused by interaction among various mechanisms. The CHM formulas, single CHM and its active components have considerable positive reports about the treatment of psoriasis, which brings hope for a promising future of CHM in the clinical therapy of psoriasis. In the paper, we have concluded that the existing therapeutic mechanisms of CHM in the treatment of psoriasis.

Antitumor and immunomodulatory activities of total flavonoids extract from persimmon leaves in H22 liver tumor-bearing mice.

Persimmon (Diospyros kaki L.) leaves are commonly used in Asia as tea infusion and as an agent in traditional medicine. The present study aims to explore the antitumor and immunomodulatory effects of total flavonoids extract from persimmon leaves (PLF) in H22 liver tumor-bearing mice. We found that the PLF showed significant inhibition on the liver tumor growth in mice with a tumor inhibition rate of up to 49.35%. In contrast to the severe side effects of cyclophosphamide (CTX), the PLF exhibited anti-cachexia effect and showed no alternation in the body weight and food intake in mice. Moreover, compared with the vehicle control and CTX group, the PLF significantly enhanced the thymus and spleen indices, level of serum interleukin-18 (IL-18), monocyte/macrophage phagocytosis, level of serum hemolysin, and activity of natural killer (NK) cells. This study demonstrated that the PLF could effectively inhibit liver tumor growth in vivo via enhancement of the immune function in mice, and it displayed the potential to be a safe and effective anticancer agent or functional immune-enhancing agent.