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.

Two new physalins from Physalis alkekengi L. var. franchetii (Mast.) Makino.

Two new physalins, 7α-hydroxy-5-deoxy-4-dehydrophysalin IX (1) and 5-deoxy-4-dehydrophysalin IX (2), together with six known compounds, luteolin (3), luteolin-7-O-glucoside (4), neoechinulin A (5), 3-(4-hydroxy-3-methoxyphenyl)-N-(4-methylphenyl)-2-propenamide (6), physalin D (7) and blumenol A (8) were isolated from Physalis alkekengi L. var. franchetii (Mast.) Makino. Their structures were elucidated by NMR spectroscopic analysis, HR-ESI-MS, X-ray crystallographic data analysis and comparison with the known compounds. Among them, compounds 5 and 6 were isolated from the genus Physalis for the first time. Compound 1 exhibited weak NAD(P)H: quinone reductase (QR) inducing activity.

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.

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.

Therapeutic Potential of Salviae Miltiorrhizae Radix et Rhizoma against Human Diseases Based on Activation of Nrf2-Mediated Antioxidant Defense System: Bioactive Constituents and Mechanism of Action.

Oxidative stress plays a central role in the pathogenesis of many human diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating the intracellular antioxidant response and is an emerging target for the prevention and therapy of oxidative stress-related diseases. Salviae Miltiorrhizae Radix et Rhizoma (SMRR) is a traditional Chinese medicine (TCM) and is commonly used for the therapy of cardiac cerebral diseases. Cumulative evidences indicated that the extract of SMRR and its constituents, represented by lipophilic diterpenoid quinones and hydrophilic phenolic acids, were capable of activating Nrf2 and inhibiting oxidative stress. These bioactive constituents demonstrated a therapeutic potential against human diseases, exemplified by cardiovascular diseases, neurodegenerative diseases, diabetes, nephropathy, and inflammation, based on the induction of Nrf2-mediated antioxidant response and the inhibition of oxidative stress. In the present review, we introduced the SMRR and Nrf2 signaling pathway, summarized the constituents with an Nrf2-inducing effect isolated from SMRR, and discussed the molecular mechanism and pharmacological functions of the SMRR extract and its constituents.