Introduction: Adipose tissue-derived stromal cells (ADSCs) are abundant and easy to obtain, but the diversity of differentiation potential from different locations may vary with the developmental origin of their mesenchymal compartment. We therefore aim to compare the myogenic differentiation and reparative activity of ADSCs derived from the pericardial tissue to ADSCs of subcutaneous origin. Methods: Pericardial and inguinal adipose tissues from Wistar rats were surgically obtained, and the stromal fraction was isolated after enzymatic digestion. The phenotypic epitopes of the resultant two types of ADSCs were analyzed with flow cytometry, and the expression of transcriptional factors was analyzed with immunostaining. Furthermore, their potential toward adipogenic, osteogenic, and myogenic differentiation also was compared. Finally, the reparative activity and the resultant functional benefits were examined by allograft transplantation into an infarcted model in rats. Results: ADSCs from two adipose sources showed identical morphology and growth curve at the initial stage, but inguinal ADSCs (ingADSCs) sustained significantly vigorous growth after 25 days of cultivation. Although both ADSCs shared similar immunophenotypes, the pericardial ADSCs (periADSC) intrinsically exhibited partial expression of transcription factors for cardiogenesis (such as GATA-4, Isl-1, Nkx 2.5, and MEF-2c) and more-efficient myogenic differentiation, but less competent for adipogenic and osteogenic differentiation. After in vivo transplantation, periADSCs exhibited significantly vigorous reparative activity evidenced by thickening of ventricular wall and pronounced vasculogenesis and myogenesis, although the majority of prelabeled cells disappeared 28 days after transplantation. The structural repair also translated into functional benefits of hearts after infarction. Conclusions: Although two sources of ADSCs are phenotypically identical, pericADSCs constituted intrinsic properties toward myogenesis and vasculogenesis, and thus provided more potent reparative effects after transplantation; therefore, they represent an attractive candidate cell donor for cardiac therapy.

Plant-derived natural compounds are widely used as alternative medicine in healthcare throughout the world. Ginkgolic acids, the phenolic compounds isolated from the leaves and seeds of Ginkgo biloba, are among the chemicals that have been explored the most. Ginkgolic acids exhibit cytotoxic activity against a vast number of human cancers in various preclinical models in vitro and in vivo. Additionally, the pharmacological activities of ginkgolic acids are also involved in antidiabetic, anti-bacteria, anti-virus, anti-fibrosis, and reno/neuroprotection. Autophagy as a highly conserved self-cleaning process that plays a crucial role in maintaining cellular and tissue homeostasis and has been proven to serve as a protective mechanism in the pathogenesis of many diseases, including neurodegenerative diseases, cancer, and infectious diseases. In this review, we surveyed the pharmacological activities of the major three forms of ginkgolic acids (C13:0, C15:1, and C17:1) that are linked to autophagic activity and the mechanisms to which these compounds may participate. A growing body of studies in last decade suggests that ginkgolic acids may represent promising chemical compounds in future drug development and an alternative remedy in humans.

Ginkgol C17:1 has been shown to inhibit apoptosis and migration of cancer cells, but the underlying mechanisms are not fully elucidated. In this study, we explored whether the inhibitory effects of Ginkgol C17:1 were associated with epidermal growth factor receptor (EGFR) and PI3K/Akt signaling. The results showed that EGF treatment increased the phosphorylation of EGFR, PI3K, Akt, mTOR and NF-kB, and also enhanced the proliferation, migration and invasion of HepG2 cells. Ginkgol C17:1 dose-dependently inhibited EGF-induced phosphorylation/activation of all the key components including EGFR, PI3K, Akt, mTOR and NF-kB, leading to a significant reduction either of proliferation or migration and invasion of HepG2 cells. Notably, treatment with Ginkgol C17:1 in mice suppressed the growth of tumor massin vivo, and expression of EGFR in the tumor tissue. The results suggest that Ginkgol C17:1 is a potent tumor inhibiting compound that acts on EGF-induced signal transduction of the PI3K/Akt signaling pathways, and may represent a clinically interesting candidate for cancer therapy.

Ginkgol C17:1 is a bioactive compound derived from Ginkgo biloba. In the present study, the effect and possible mechanisms of action of Ginkgol C17:1 on the biological behaviors of tumor cells were investigated. Whilst cell proliferation was assessed using the MTT assay, the behaviors of cell migration and invasion were explored using Transwell and modified Transwell assays. The results revealed that Ginkgol C17:1 significantly inhibited the proliferation, migration and invasion of human tumor cells in a dose-dependent manner. Furthermore, due to their associations with the biological behaviors of tumor cells, the protein expression of matrix metalloproteinase (MMP)-7, Ras homolog gene family, member A (RhoA) and phosphorylated-protein kinase B (Akt) was analyzed by western blotting. The results showed that the expression of the aforementioned proteins was decreased markedly following Ginkgol C17:1 treatment. The results of the present study suggested that Ginkgol C17:1 suppresses the biological behaviors of tumor cells by inhibiting the activation of the mitogen-activated protein kinase/MMP, Rho/Rho-associated protein kinase and phosphatidylinositol 3-kinase/Akt signaling pathways.

Liver cancer is a major healthcare problem and one of the leading causes of cancer‑associated mortality in the world. To date, chemotherapy remains a common method for treating cancer and cisplatin is one of the most widely used chemotherapeutics. However, owing to drug resistance and side effects, it is imperative to identify a novel approach to improve the anticancer effect of cisplatin. Auxiliary chemotherapy drugs with minor toxicity to normal cells may represent a novel strategy for cancer therapy. Previous studies have indicated that ginkgol C17:1 exhibits anticancer effects in liver cancer cells in vitro and in vivo. The antitumor activity of ginkgol C17:1 has been reported in combination with cisplatin in human liver cancer cells. Owing to the route of systemic administration, liver cancer cells and normal hepatocytes were exposed to chemotherapeutics and auxiliary chemotherapy drugs. However, the effects of ginkgol C17:1 in normal hepatocytes remain unclear. In the present study, the biological effects of ginkgol C17:1 alone and as co‑treatment with cisplatin were compared in human hepatoma cells and normal hepatocytes. Consistently, the results confirmed that in human hepatoma HepG2 cells, ginkgol C17:1 or cisplatin alone induced autophagy and apoptosis. The co‑treatment increased cisplatin‑induced apoptosis and inhibited cisplatin‑induced autophagy. In comparison, the treatments in human normal L02 hepatocytes indicated that ginkgol C17:1 alone induced autophagy, whereas cisplatin alone induced apoptosis. The co‑treatment inhibited cisplatin‑induced apoptosis, but enhanced autophagy in L02 cells. Further investigation revealed that the AMP‑activated protein kinase/serine/threonine protein kinase ULK1 and phosphoinositide 3‑kinase/protein kinase B/mammalian target of rapamycin signaling pathways were involved in the underlying regulatory mechanisms. Taken together, the results of the present study provide the first evidence that ginkgol C17:1 protects normal hepatocytes against cisplatin‑induced cytotoxicity while potentiating the anticancer effect of cisplatin chemotherapy. The differential effects on normal and cancer cells suggest that ginkgol C17:1 is a promising candidate for auxiliary chemotherapy.