Withanolides from the active extract of Physalis angulate and their anti-hepatic fibrosis effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Physalis angulata L., a traditional Chinese medicine called "Kuzhi" in China, was used traditionally to treat liver diseases (eg. icterus, hepatitis) as well as malaria, asthma, and rheumatism. AIM OF THE STUDY: Our study aimed to investigate the withanolides with anti-hepatic fibrosis effect from P. angulate. MATERIALS AND METHODS: Withanolides were obtained from the EtOH extract of P. angulate by bioassay-molecular networking analysis-guided isolation using column chromatography and normal/reversed-phase semipreparative HPLC. The structures of new withanolides were elucidated by combinations of spectroscopic techniques with NMR and ECD calculations. MTT cell viability assay, AO/EB staining method, cell wound healing assay, ELISA and Western blot experiments were employed to evaluate the anti-hepatic fibrosis activity and to uncover related mechanism. Molecular docking analysis and cellular thermal shift assay were used to evaluate and verify the interaction between the active withanolides and their potential targets. RESULTS: Eight unreported withanolides, withagulides A-H (1-8), along with twenty-eight known ones were obtained from P. angulate. Withanolides 6, 9, 10, 24, 27, and 29-32 showed marked anti-hepatic fibrosis effect with COL1A1 expression inhibition above 50 %. Physalin F (9), the main component in the active fraction, significantly decreased the TGF ß1-stimulated expressions of collagen I and α-SMA in LX-2 cells. Mechanism study revealed that physalin F exerted its anti-hepatic fibrosis effect via the PI3K/AKT/mTOR signaling pathway. CONCLUSION: This study suggested that withanolides were an important class of natural products with marked anti-hepatic fibrosis effect. The main withanolide physalin F might be a promising candidate for hepatic fibrosis treatment. The work provided experimental foundation for the use of P. angulate to treat hepatic fibrosis.

Application of targeted drug delivery system in Chinese medicine.

Targeted drug delivery system of traditional Chinese medicine (TCM) refers to those using different carriers to make the effective parts or monomer extracted from TCM or natural medicine into agents which can directly concentrate on the target site. This system is an ideal delivery approach and has became a hot spot in the field of TCM pharmaceutical research since it can improve the pharmacological effects and reduce the adverse reactions. This paper reviews literatures on TCM targeted agents which were published in the past 10 years. In accordance with the different carriers, four types of agents, liposome, nanoparticle, microsphere, and emulsion are analyzed. Liposomes were studied most profoundly and a variety of new types of liposomes was developed on the basis of the traditional liposomes. Using natural or synthetic polymer materials to carry drugs, nanoparticles and microspheres can promote the drug through the blood-brain barrier and enhance its bioavailability. Emulsion has lymphatic affinity and the drug is coated in the internal phase, which can protect the drugs from hydrolysis. All these delivery agents are proved to be effective ways to improve the clinical efficacy of drugs, and each is discussed in detail with examples. At present, TCM targeted agents are still in the exploratory stage and many problems need to be solved. Especially, it is a huge challenge to research the targeted delivery systems for the effective parts of Chinese medicines and compound prescriptions, and the paper gives a particular discussion on this point. In the future, more attention should be paid to the research on the particle agents of TCM effective parts, and the development of new carrier materials in order to enhance the overall quality of TCM targeted agents.

Optimization of cross-linking parameters during production of transglutaminase-hardened spherical multinuclear microcapsules by complex coacervation.

Gelatin-gum arabic spherical multinuclear microcapsules (SMMs) encapsulating peppermint oil were prepared by complex coacervation. Transglutaminase (TG) was used to harden the SMMs by complex coacervation instead of traditional reagents such as formaldehyde or glutaraldehyde. The effect of various cross-linking parameters on the hardening effectiveness of SMMs containing peppermint oil was investigated. The optimum parameters were as follows: hardening for 6h at 15 degrees C and pH 6.0 with a TG concentration of 15 U/g gelatin. Compared with formaldehyde, TG exhibits similar microcapsule hardening effectiveness.