The ethanol extract of flower buds of Tussilago farfara L. attenuates cigarette smoke-induced lung inflammation through regulating NLRP3 inflammasome, Nrf2, and NF-κB.

ETHNOPHARMACOLOGICAL RELEVANCE: The flower buds of Tussilago farfara L. (Abbreviated as FTF) were widely used in traditional Chinese medicine (TCM) to treat respiratory diseases, including asthma, dry throat, great thirst, turbid saliva, stinky pus, and coughs caused by various causes. AIM OF STUDY: The aim of study is to explore the efficiency of FTF in vitro and in vivo for the treatment of lung inflammation, and to illustrate the possible mechanisms of FTF in treating inflammation-related respiratory diseases targeting NOD-like receptor 3 (NLRP3) inflammasome, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear transcription factor-κB (NF-κB). METHODS: Lung inflammation model in vivo was induced by exposure of mice to cigarette smoke (CS) for two weeks. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), inflammatory factors, and histology in lung tissues were investigated in presence or absence of ethanol extract of the flower buds of T. farfara L. (FTF-EtOH). In the cell-based models, nitric oxide (NO) assay, flow cytometry assay, enzyme-linked immunosorbent assay (Elisa), and glutathione (GSH) assay were used to explore the anti-inflammatory and anti-oxidant effects of FTF-EtOH. Possible anti-inflammatory mechanisms of FTF targeting NLRP3 inflammasome, Nrf2, and NF-κB have been determined using western blot, quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), immunofluorescence assay, nuclear and cytoplasmic extraction, and ubiqutination assay. RESULTS: FTF-EtOH suppressed CS-induced overproduction of inflammatory factors [e.g., tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß)], and upregulation of the content of intracellular MDA in the lung homogenate of mice. In cell-based models, FTF-EtOH reduced the lipopolysaccharide (LPS)-induced overproduction of inflammatory factors, and attenuated the CS extract-induced overgeneration of reactive oxygen species (ROS). Furthermore, FTF-EtOH up-regulated Nrf2 and its downstream genes through enhancing the stability of Nrf2 protein, and inhibited the activation of NF-κB and NLRP3 inflammasome, which have been confirmed by detecting the protein levels in the mouse model. CONCLUSIONS: FTF-EtOH effectively attenuated lung inflammation in vitro and in vivo. The protection of FTF-EtOH against inflammation was produced by activation of Nrf2 and inhibitions of NF-κB and NLRP3 inflammasome. These datas definitely support the ethnopharmacological use of FTF as an anti-inflammatory drug for treating respiratory diseases in TCM.

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 the Rhizome of Ligusticum chuanxiong Hort. and Their Nrf2 Inducing Activity.

The rhizome of Ligusticum chuanxiong Hort. has been widely used for the therapy of diabetic nephropathy (DN) in traditional Chinese medicine (TCM). The nuclear transcription factor erythroid 2-related factor (Nrf2) is a potential target for treating DN. The purpose of this research was to study the chemical constituents from the rhizome of L. chuanxiong, evaluate their Nrf2 inducing activity, and find the molecules with potential therapeutic effect against DN. In this study, two new phthalides (1-2) along with twenty-seven known constituents were obtained from the rhizome of L. chuanxiong. Their structures were elucidated through various spectroscopic methods. Twelve constituents, including eight phthalides (2, 5, 6,10-13, 14) and four other compounds (17, 18, 20,28), stimulated NAD(P)H: quinone reductase (QR) activity, suggesting that these bioactive constituents were potential Nrf2 activators. Among the isolated compounds, phthalide levistolide A (LA, 14) upregulated the protein levels of Nrf2, NQO1, and γ-GCS in a dose-dependent manner. Our results implied that the clinical application of the rhizome of L. chuanxiong as an anti-DN drug in TCM might be attributed to the Nrf2 inducing effect of phthalides. Thus, phthalides is a group of promising leading molecules for discovering anti-DN agents.

Thesium chinense Turcz.: An ethnomedical, phytochemical and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Thesium chinense Turcz. has been used to treat mastitis, pulmonitis, tonsillitis, iaryngopharyngitis and upper respiratory tract infections in the indigenous medicine of China for a long history. Presently, several pharmaceutics prepared by this medical herb have been clinically used for the therapy of infectious diseases. AIM OF THE REVIEW: This review aims to comprehensively summarize the current researches on the ethnomedical, phytochemical and pharmacological aspects of T. chinense, and discuss their possible opportunities for the future research. MATERIALS AND METHODS: Extensive database searches, including Web of Science, SciFinder, Google Scholar and China Knowledge Resource Integrated, were performed using keywords such as 'Thesium chinense', 'Bai Rui Cao', and their chemical constituents. In addition, local classic herbal literature on ethnopharmacology and relevant textbooks were consulted to provide a comprehensive survey of this ethnomedicine. RESULTS: Thirty four chemical constituents, including flavonoids, alkaloids, and terpenoids, have been identified from T. chinense. Of which, flavonoids are the predominant and characteristic constituents. The crude extracts, the purified constituents, and commercial available pharmaceutics have displayed diverse in vitro and in vivo pharmacological functions (e.g. anti-inflammation, antimicrobial activity, analgesic effect, hepaprotection), and are particularly useful as a potential therapeutic agent against inflammation-related diseases. CONCLUSIONS: T. chinense is an important ethnomedical medicine and possesses a satisfying effect for treating inflammation, microbial infection, and upper respiratory diseases. It has received plenty of researches on its phytochemical and pharmacological aspects since 1970s. These findings definitely establish the link between chemical composition and pharmacological application, and support the ethnomedical use of T. chinense in the indigenous medicine of China. However, chemical composition of this plant and the molecular mechanisms of purified constituents have not been comprehensively investigated, and thus the trace constituents and the therapeutic targets of bioactive constituents deserve a further exploration. Collectively, the researchers should pay more attention to a better understanding and application of this ethnomedical plant.

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.