The alleviative effect of flavonol-type Nrf2 activator rhamnazin from Physalis alkekengi L. var. franchetii (Mast.) Makino on pulmonary disorders.

Rhamnazin (RN) is a flavonol isolated from the calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino, which has been used for treating pulmonary diseases in traditional Chinese medicine. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a therapeutic target for pulmonary diseases. In the present study, the underlying mechanism and pharmacological effect of RN against pulmonary disorders are investigated. Human lung epithelial Beas-2B cell and RAW 264.7 murine macrophage-based cell models, and a cigarette smoke (CS)-induced pulmonary impairment mice model are adopted for investigation in vitro and in vivo. RN is identified to be an Nrf2 activator, which promotes Nrf2 dissociation from Keap1 via reacting with the Cys151 cysteine residue of Keap1, and suppresses Nrf2 ubiquitination. In addition, RN is able to attenuate toxicant-stimulated oxidative stress and inflammatory response in vitro. Importantly, RN significantly relieves CS-induced oxidative insult and inflammation, and RN-induced inhibition of inflammation is related to inhibition of nuclear transcription factor-κB (NF-κB) and induction of cell autophagy. In conclusion, our data indicate that RN is an activator of the Nrf2 pathway and evidently alleviates pulmonary disorders via restricting NF-κB activation and promoting autophagy. RN is a promising candidate for the therapy of pulmonary disorders.

Chemical Constituents from Physalis Calyx seu Fructus and Their Inhibitory Effects against Oxidative Stress and Inflammatory Response.

Physalis Calyx seu Fructus, a traditional Chinese medicine consisting of the calyxes and fruits of Physalis alkekengi var. franchetii, has been used as therapy for inflammation-related respiratory diseases such as excessive phlegm, cough, sore throat, and pharyngitis for a long history in China. The aim of the present study was to investigate the chemical constituents of Physalis Calyx seu Fructus and identify the bioactive constituents responsible for its traditional application as therapy for inflammation-related diseases. In the present study, one new phenylpropanoid (1: ), two new steroids (17: and 18: ), together with 55 known constituents have been purified from the EtOH extract of Physalis Calyx seu Fructus. Among them, seven and twelve known constituents were isolated for the first time from Physalis Calyx seu Fructus and the genus Physalis, respectively. Fourteen constituents, including steroids [physalins (5:  - 9, 12:  - 14: , and 15: ) and ergostane (21: )], a sesquiterpenoid (35: ), alkaloids (36: and 37: ), and a flavonoid (44: ), showed inhibitory effects against oxidative stress. Ten constituents, including steroids (5, 6, 8, 13: , and 15: ), sesquiterpenoids (34: and 35: ), alkaloids (37: and 41: ), and a flavonoid (43: ), were found be potential anti-inflammatory constituents of this medicinal plant. The inhibition of oxidative stress and inflammatory response may be related to the regulation of Nrf2 and nuclear factor-κB pathways. The ethnomedical use of Physalis Calyx seu Fructus as a treatment for respiratory diseases might be attributed to the combined inhibitory effects of steroids, alkaloids, sesquiterpenoids, and flavonoids against oxidative stress and inflammatory response.

4ß-Hydroxywithanolide E from Goldenberry (Whole Fruits of Physalis peruviana L.) as a Promising Agent against Chronic Obstructive Pulmonary Disease.

Environmental toxicant- and oxidant-induced [e.g., cigarette smoke (CS)] respiratory oxidative stress and inflammatory response play a vital role in the onset and progression of COPD. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents an important mechanism for regulating intracellular oxidative stress and inflammatory response and is a promising target for developing agents against COPD. Herein, a bioactivity-guided purification of goldenberry (whole fruits of Physalis peruviana L.) led to the isolation of a novel and potent Nrf2 activator 4ß-hydroxywithanolide E (4ß-HWE). Our study indicated that (i) 4ß-HWE activated the Nrf2-mediated defensive response through interrupting Nrf2-Keap1 protein-protein interaction (PPI) via modification of Cys151 and Cys288 cysteine residues in Keap1 and accordingly suppressing the ubiquitination of Nrf2. (ii) 4ß-HWE enhanced intracellular antioxidant capacity and inhibited oxidative stress in normal human lung epithelial Beas-2B cells and wild-type AB zebrafish. (iii) 4ß-HWE blocked LPS-stimulated inflammatory response and inhibited LPS-stimulated NF-κB activation in RAW 264.7 murine macrophages. (iv) 4ß-HWE effectively suppressed oxidative stress and inflammatory response in a CS-induced mice model of pulmonary injury. Collectively, these results display the feasibility of using 4ß-HWE to prevent or alleviate the pathological progression of COPD and suggest that 4ß-HWE is a candidate or a leading molecule against COPD.

Withanolides from the genus Physalis: a review on their phytochemical and pharmacological aspects.

OBJECTIVES: Withanolides are a group of modified C28 ergostane-type steroids with a C-22, C-26 δ-lactone side chain or a C-23, C-26 γ-lactone side chain. They enjoy a limited distribution in the plant kingdom and predominantly occur in several genera of Solanaceae. Of which, the genus Physalis is an important resource for this type of natural molecules. The present review aims to comprehensively illustrate the structural characteristics and classification of withanolides, and particularly focus on the progression on phytochemical and pharmacological aspects of withanolides from Physalis ranging from January 2015 to June 2019. KEY FINDINGS: Approximately 351 natural withanolides with novel and unique structures have so far been identified from genus Physalis, mainly isolated from the species of P. angulata and P. peruviana. Withanolides demonstrated diverse biological activity, such as anticancer, anti-inflammatory, antimicrobial, immunoregulatory, trypanocidal and leishmanicidal activity. Their observed pharmacological functions supported the uses of Physalis species in traditional or folk medicines. SUMMARY: Due to their unique structure skeleton and potent bioactivities, withanolides are regarded to be promising drug candidates, particularly for developing anticancer and anti-inflammatory agents. Further investigations for discovering novel withanolides of genus Physalis, exploiting their pharmacological values and evaluating their potency as therapeutic agents are significant work.

Two new p-terphenyl derivatives from the marine fungal strain Aspergillus sp. AF119.

Two new p-terphenyl derivatives (1, 2), together with six known ones (3-8), have been isolated from the marine fungal strain Aspergillus sp. AF119. The structures for terphyl acid (1) and terphyl diacid (2) were determined on the basis of HR Q-TOF-MS, and 1D- and 2D-NMR spectroscopic data. The in vitro cytotoxic activities of compounds 1-8 were tested against human tumor cell lines HeLa, HepG-2 and MDA-MB-435; only compounds 5-8 exhibited inhibitory activity against the tested cell lines with IC50 values < 20 microM. Moreover, compound 5 showed a mechanism of inducing cell cycle arrest and apoptosis mediated by the generation of ROS and subsequent DNA double-strand break.

Phaeochromycins F-H, three new polyketide metabolites from Streptomyces sp. DSS-18.

Three new polyketides, phaeochromycins F (1), G (2), H (3), were obtained from the culture broth of marine actinomycete strain Streptomyces sp. DSS-18. Their structures were established on the basis of detailed spectroscopic analyses, including 1D-, 2D-NMR and HR-ESI MS techniques.