Progress on the mechanism of natural products alleviating androgenetic alopecia.

Androgenetic alopecia (AGA) has become a widespread problem that leads to considerable impairment of the psyche and daily life. The currently approved medications for the treatment of AGA are associated with significant adverse effects, high costs, and prolonged treatment duration. Therefore, natural products are being considered as possible complementary or alternative treatments. This review aims to enhance comprehension of the mechanisms by which natural products treat AGA. To achieve this, pertinent studies were gathered and subjected to analysis. In addition, the therapeutic mechanisms associated with these natural products were organized and summarized. These include the direct modulation of signaling pathways such as the Wnt/ß-catenin pathway, the PI3K/AKT pathway, and the BMP pathway. Additionally, they exert effects on cytokine secretion, anti-inflammatory, and antioxidant capabilities, as well as apoptosis and autophagy. Furthermore, the review briefly discusses the relationship between signaling pathways and autophagy and apoptosis in the context of AGA, systematically presents the mechanisms of action of existing natural products, and analyzes the potential therapeutic targets based on the active components of these products. The aim is to provide a theoretical basis for the development of pharmaceuticals, nutraceuticals, or dietary supplements.

Tumor Microenvironment-Responsive Theranostic Nanoplatform for in Situ Self-Boosting Combined Phototherapy through Intracellular Reassembly.

Through rational design, in vivo supramolecular construction of nanodrugs could precisely proceed in the lesion areas, which may apparently improve the theranostic performance of nanomaterials. Herein, a tumor microenvironment-responsive theranostic nanoplatform (Ce6-GA@MnO2-HA-PEG) has been constructed to achieve in vivo supramolecular construction and enhance the therapeutic efficacy of combined phototherapy through intracellular reassembly. Under the tumor microenvironment, such nanoplatform could undergo the process of decomposition-reassembly and form in situ photothermal assemblies. The generation of assemblies would endow this nanoplatform with the capacity of photothermal therapy. Meanwhile, this nanoplatform could alleviate hypoxia and improve the therapeutic efficacy of photodynamic therapy. The results of in vitro and in vivo experiments reveal that tumors can be ablated efficiently by the designed nanoplatform under laser irradiation. In addition, fluorescence imaging and magnetic resonance imaging can be activated by the decomposition of MnO2 to realize tumor imaging in vivo. Therefore, this multifunctional nanoplatform exhibits the capacity for boosting dual-modal imaging-guided combined phototherapy through intracellular reassembly, which may propose a new thought in cancer theranostics.

Design and synthesis of novel C14-urea-tetrandrine derivatives with potent anti-cancer activity.

Tetrandrine is a dibenzyltetrahydroisoquinoline alkaloid, isolated from traditional Chinese medicinal plant Stephania tetrandra, with anti-tumor activity. Our previous study identified several derivatives of tetrandrine showing better activities than parental compound against human hepatocellular carcinoma cells. To increase diversity and cytotoxic activities of the original compound, a series of novel 14-urea-tetrandrine derivatives were synthesized through structural modification of tetrandrine. These derivaties demonstrated a moderate to strong anti-proliferative activities against human cell lines HEL and K562 (Leukemia), prostate (PC3), breast (MDA-MB-231) and melanoma (WM9). Compound 4g showed strongest cytotoxic effect against PC3 cells with IC50 value of 0.64 µM, which was 12-fold, 31-fold and 26-fold lower than the parental tetrandrine, 5-fluorouracil and cisplatin, respectively. Preliminary structure-activity relationship study indicated that urea subsititution was the key pharmacophore for the enhancement of their antitumor activities. Induction of apoprosis by 4g was associated with the activation of pro-apoptotic protein BAX and inhibition of antiapoptosis proteins survivin as well as Bcl-2. Moreover, activation of caspases led to increase cleavage of PARP, which further accelerates apoptotic cell death. These results reveal that the compound 4g may be used as a potential anticancer drug candidate.

Design and synthesis of novel tetrandrine derivatives as potential anti-tumor agents against human hepatocellular carcinoma.

Tetrandrine, a lead anti-tumor compound with a bis-benzyltetrahydroisoquinoline skeleton isolated from medicinal plant Stephania tetrandra. In order to obtain active anti-tumor agents and evaluate their structure-activity relationships, a series of novel tetrandrine derivatives were designed and synthesized in this study. Their anti-tumor activities against human hepatocellular carcinoma cell lines (HMCC97L and PLC/PRF/5) were also evaluated. The bioassay results showed that the derivatives exhibited moderate to strong inhibition against the two cell lines. Among them, compound 31 showed prominent cytotoxicity with IC50 = 1.06 µM (15.8 folds than that of tetrandrine, and 30.3 folds than that of Sorafenib). Further studies on the mechanisms demonstrated that the in vitro anti-tumor activity of compound 31 was predominantly due to the inducement of apoptosis of HCC cells. Compound 31 was capable of initiating endoplasmic reticulum stress-associated apoptotic cell death, and the activation of JNK as well as caspase pathways were probably involved. Our results suggest that compound 31, a new 14-position substituted amide tetrandrine derivative, might be a potential candidate for developing novel anti-HCC drugs in the coming future.