We established myocardial injury models in vivo and in vitro to investigate the cardioprotective effect of gomisin D obtained from Schisandra chinensis. Gomisin D significantly inhibited isoproterenol-induced apoptosis and hypertrophy in H9C2 cells. Gomisin D decreased serum BNP, ANP, CK-MB, cTn-T levels and histopathological alterations, and inhibited myocardial hypertrophy in mice. In mechanisms research, gomisin D reversed ISO-induced accumulation of intracellular ROS and Ca2+. Gomisin D further improved mitochondrial energy metabolism disorders by regulating the TCA cycle. These results demonstrated that gomisin D had a significant effect on isoproterenol-induced myocardial injury by inhibiting oxidative stress, calcium overload and improving mitochondrial energy metabolism.

Platelet-derived growth factor receptor β (PDGFRβ) plays an important role in hepatic fibrosis and is closely associated with hepatic stellate cells (HSCs) activation. Previously, by modeling PDGFRβ affinity chromatography, we found that gomisin D can target PDGFRβ. However, whether gomisin D has anti-fibrosis effects through targeting PDGFRβ remained unclear. In this study, the effect of gomisin D on hepatic fibrosis was evaluated in vivo and vitro. HSC cell lines and primary HSC were cultured and functionally we found that gomisin D promotes HSC apoptosis, inhibits HSCs activation and proliferation. A male BALB/c mouse liver fibrosis model was established to comfirm gomisin D (especially in 50 mg/kg) could improve liver fibrosis by inhibiting HSCs activation. In addition, gomisin D had a good binding ability with PDGFRβ (KD = 3.3e-5 M). Mechanically, gomisin D regulated PDGF-BB/PDGFRβ signaling pathway by targeting PDGFRβ, further more inhibited HSC activation, subsequently inhibited inflammatory factors, ultimately improved CCl4-induced liver fibrosis. Overall, gomisin D could inhibit HSC proliferation and activation, promote HSC apoptosis, and alleviate CCl4-induced hepatic fibrosis by targeting PDGFRβ and regulating PDGF-BB/PDGFRβ signaling pathway. This study provides a new drug for anti-liver firbosis therapy, and elucidates the deeper mechanism of gomisin D against HSCs activation by targeting PDGFRβ.

Skin cancer is the most common human malignancy worldwide and solar ultraviolet (UV) radiation is known to serve an important role in its pathogenesis. Natural candidate compounds with antioxidant, photoprotective and anti‑melanogenic effects were investigated against the background of skin photoprotective and anti‑melanogenic properties. Gomisin D, J and O are dibenzocyclooctadiene lignans present in Kadsura medicinal plants and possess several pharmacological activities. In this study, the functions and mechanisms underlying the effects of gomisin D, J and O in UVA‑and UVB‑irradiated keratinocytes and α‑melanocyte stimulating hormone (α‑MSH)‑stimulated melanocytes were explored. Following UVA and UVB irradiation, keratinocytes were treated with gomisin D, J and O, and keratinocyte viability, lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) production and apoptosis were examined. The results demonstrated that gomisin D and J improved keratinocyte viability and reduced LDH release under UVA and UVB irradiation. Intracellular ROS production induced by UVA and UVB irradiation was suppressed by gomisin D and J. In addition, Annexin V and TUNEL staining analysis indicated that gomisin D and J have significant anti‑apoptotic effects on UVA‑and UVB‑irradiated keratinocytes. After α‑MSH stimulation, melanocytes were treated with gomisin D, J and O, and the changes in melanocyte viability, intracellular melanin content, intracellular tyrosinase activity, and mechanisms underlying these changes were examined. Gomisin D markedly inhibited the α‑MSH‑induced increase in intracellular melanin content and tyrosinase activity. Mechanistically, gomisin D reduced the protein and mRNA expression levels of microphthalmia‑associated transcription factor (MITF), tyrosinase, tyrosinase‑related protein (TRP)‑1 and TRP‑2 in α‑MSH‑stimulated melanocytes. In addition, gomisin D markedly downregulated α‑MSH‑induced phosphorylation of protein kinase A and cAMP response element binding protein, which are known to be present upstream of the MITF, tyrosinase, TRP‑1 and TRP‑2 genes. Overall, gomisin D has photoprotective and anti‑melanogenic effects; these findings provide a basis for the production of potential brightening and photoprotective agents using natural compounds such as gomisin D.

Gomisin D, a lignan compound isolated from Fructus Schisandra, is a potential antidiabetic and anti-Alzheimer\'s agent. Recently, gomisin D was used as a quality marker of some traditional Chinese medicine (TCM) formulas. In this study, a rapid ultra-performance liquid chromatography/tandem mass spectrometry method (UPLC-MS/MS) was developed and validated to quantify gomisin D in rat plasma for a pharmacokinetic and bioavailability study. Acetonitrile was used to precipitate plasma proteins. Separations were performed on a BEH C18 column with a gradient mobile phase comprising of acetonitrile and water (0.1% formic acid). An electrospray ionization source was applied and operated in the positive ion mode. The multiple reaction monitoring mode (MRM) was utilized to quantify gomisin D and nomilin (internal standard, IS) using the transitions of m/z 531.2 → 383.1 and m/z 515.3 → 161.0, respectively. The calibration curve was linear over the working range from 1 to 4000 ng/mL (R² = 0.993). The intra- and interday precision ranged from 1.9% to 12.9%. The extraction recovery of gomisin D was in the range of 79.2-86.3%. The validated UPLC-MS/MS method was then used to obtain the pharmacokinetic characteristics of gomisin D after intravenous (5 mg/kg) and intragastric (50 mg/kg) administration to rats. The bioavailability of gomisin D was 107.6%, indicating that this compound may become a promising intragastrical medication. Our results provided useful information for further preclinical studies on gomisin D.