Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9.

OBJECTIVE: To explore whether the ethanol extract of Herpetospermum caudigerum Wall (EHC), a Xizang medicinal plant traditionally used for treating liver diseases, can improve imiquimod-induced psoriasis-like skin inflammation. METHODS: Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice. The protein levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-17A (IL-17A) in mouse skin samples were examined using immunohistochemical staining. In vitro, IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1 (ICAM-1) and chemokine CXC ligand 9 (CXCL9) using Western blotting and reverse transcription-quantitative polymerase chain reaction. The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9. RESULTS: EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ, TNF-α, and IL-17A in psoriatic lesions. Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes. Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin-proteasome-mediated protein degradation rather than transcriptional repression. Seven primary compounds including ehletianol C, dehydrodiconiferyl alcohol, herpetrione, herpetin, herpetotriol, herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry. CONCLUSION: Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites. Please cite this article as: Zhong Y, Zhang BW, Li JT, Zeng X, Pei JX, Zhang YM, Yang YX, Li FL, Deng Y, Zhao Q. Ethanol extract of Herpetospermum caudigerum Wall ameliorates psoriasis-like skin inflammation and promotes degradation of keratinocyte-derived ICAM-1 and CXCL9. J Integr Med. 2023; 21(6): 584-592.

In vitro antioxidative activity of Fritillaria cirrhosa D. Don straw ethanolic extract and its effect on lipid, protein oxidation, and quality of Chinese-style sausage.

Fritillaria cirrhosa D. Don, which can be used for medicine and food, contains a variety of chemicals including polyphenols, alkaloids, terpenoid, and others that have beneficial biological properties like antihypertension, bacteriostasis, and anti-inflammatory. The ethanolic extract of Fritillaria straw was obtained for this study using ultrasonic-aided extraction, and the amounts of total phenols and total flavonoids were 26.56 ± 1.36 mg GAE/g dw and 18.75 ± 0.80 mg RE/g dw, respectively. Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry technology was utilized to identify 50 major chemicals in the Fritillaria straw extract (FSE). Meanwhile, the antioxidative activities of FSE were evaluated by 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and Ferric reducing antioxidant power assays in vitro, which pointed out the antioxidative potential of FSE. Additionally, 0.1%, 0.5%, and 1% of FSE and 0.02% butylated hydroxyanisole (BHA) + butylated hydroxytoluene (BHT) (1:1) were separately added to Chinese-style sausage to study their effects on the lipid oxidation, protein oxidation, and quality of the sausage at different storage times. The study found that the effect of adding 1% FSE on carbonyl content, total volatile basic nitrogen, and TVC of sausage could achieve the effect of the 0.02% BHA + BHT (1:1) group on the 35th day, and the thiobarbituric acid reactive substances value and peroxide value of sausage were significantly lower than the control group. Therefore, as one of the candidates to replace synthetic antioxidants, the FSE can be used in the production of Chinese sausages, which has a positive effect on improving the product's quality and extending the shelf life. PRACTICAL APPLICATION: The antioxidative activities of 50 main compounds were identified after the ethanolic extraction of Fritillaria straw. This Fritillaria straw extract was added to Chinese sausage, effectively inhibiting the oxidation of lipids and proteins as well as the decomposition of proteins. Obviously, the Fritillaria straw extract, one of the choices to replace synthetic antioxidants, may be useful for future meat processing, because of its positive impact on the product's quality and shelf life.

Total alkaloids of Fritillaria unibracteata var. wabuensis bulbus ameliorate chronic asthma via the TRPV1/Ca2+/NFAT pathway.

BACKGROUND: Asthma is a chronic inflammatory disease that is challenging to treat. Fritillaria unibracteata var. wabuensis (FUW) is the plant origin for the famous Chinese antitussive medicine Fritillaria Cirrhosae Bulbus. The total alkaloids of Fritillaria unibracteata var. wabuensis bulbus (TAs-FUW) have anti-inflammatory properties and may be used to treat asthma. PURPOSE: To explore whether TAs-FUW have bioactivity against airway inflammation and a therapeutic effect on chronic asthma. METHODS: The alkaloids were extracted via ultrasonication in a cryogenic chloroform-methanol solution after ammonium-hydroxide percolation of the bulbus. UPLC-Q-TOF/MS was used to characterize the composition of TAs-FUW. An ovalbumin (OVA)-induced asthmatic mouse model was established. We used whole-body plethysmography, ELISA, western blotting, RT-qPCR, and histological analyses to assess the pulmonary pathological changes in these mice after TAs-FUW treatment. Additionally, TNF-α/IL-4-induced inflammation in BEAS-2B cells was used as an in vitro model, whereby the effects of various doses of TAs-FUW on the TRPV1/Ca2+-dependent NFAT-induced expression of TSLP were assessed. Stimulation and inhibition of TRPV1 receptors by capsaicin (CAP) and capsazepine (CPZ), respectively, were used to validate the effect of TAs-FUW. RESULTS: The UPLC-Q-TOF/MS analysis revealed that TAs-FUW mainly contain six compounds (peiminine, peimine, edpetiline, khasianine, peimisine, and sipeimine). TAs-FUW improved airway inflammation and obstruction, mucus secretion, collagen deposition, and leukocyte and macrophage infiltration, and downregulated TSLP by inhibiting the TRPV1/NFAT pathway in asthmatic mice. In vitro, the application of CPZ demonstrated that the TRPV1 channel is involved in TNF-α/IL-4-mediated regulation of TSLP. TAs-FUW suppressed TNF-α/IL-4-induced TSLP generation expression by regulating the TRPV1/Ca2+/NFAT pathway. Furthermore, TAs-FUW reduced CAP-induced TSLP release by inhibiting TRPV1 activation. Notably, sipeimine and edpetiline each were sufficient to block the TRPV1-mediated Ca2+ influx. CONCLUSION: Our study is the first to demonstrate that TNF-α/IL-4 can activate the TRPV1 channel. TAs-FUW can alleviate asthmatic inflammation by suppressing the TRPV1 pathway and thereby preventing the increase in cellular Ca2+ influx and the subsequent NFAT activation. The alkaloids in FUW may be used for complementary or alternative therapies in asthma.

Chromosome-Level Genome Assembly of Herpetospermum pedunculosum (Cucurbitaceae).

This study presents a chromosome-level reference genome assembly of a traditional Tibetan medicinal plant, Herpetospermum pedunculosum belonging to the Cucurbitaceae family. Following a combined PacBio high-fidelity sequencing and Hi-C analysis, a final H. pedunculosum genome assembly, 804.11 Mb in length was obtained, 90.45% of which was anchored into ten pseudochromosomes with a contig N50 of 24.39 Mb. In addition, 579.55 Mb repetitive sequences and 23,924 high-confidence protein-coding genes were annotated. Phylogenetic analysis revealed that H. pedunculosum was sister to a clade formed by cucumber, zucchini, and wax gourd. Further whole-genome duplication analysis revealed no recent polyploidization event in the H. pedunculosum genome. The high-quality H. pedunculosum genome presented here will be highly useful in investigating the molecular mechanisms underlying the biosynthesis of its active compounds and adaptation strategies to the extreme environment. It will also provide great insights into comparative genomic studies of Cucurbitaceae and flowering plants.

Water extract from Herpetospermum pedunculosum attenuates oxidative stress and ferroptosis induced by acetaminophen via regulating Nrf2 and NF-κB pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Herpetospermum pedunculosum seeds is a traditional Tibetan medicine possessing hepatoprotective effect, but their protective effect on APAP-induced liver injury has not yet been explored. AIM OF THE STUDY: This study aimed at exploring the protective effect and mechanism of the water extract from the seeds of Herpetospermum pedunculosum (HPWE) on APAP-induced liver injury in vitro and in vivo. MATERIALS AND METHODS: In vitro and in vivo models of liver injury were established by APAP treatment of BRL-3A cells or mice. The effect and mechanism of action of HPWE were explored by using cell viability assay, ELISA, immunofluorescence assay, RT-qPCR, histological observation and immunohistochemistry staining, western blotting and high-content imaging system. RESULTS: In vitro experiments showed that HPWE treatment significantly promoted the cell viability, decreased ALT/AST level, and inhibited the ROS accumulation induced by APAP. Furthermore, HPWE and Fer-1 alleviated erastin-induced cell ferroptosis, upregulated GPX4 and SLC7A11 expression, and reduced lipid peroxides production. Further study showed that APAP could also downregulate the expression of GPX4 and SLC7A11, causing cell ferroptosis, and HPWE and Fer-1 counteracted this process. Our in vivo experiments showed that pretreatment with HPWE in APAP-treated mice significantly alleviated the serum ALT/AST level, decreased necrotic cells and inflammatory cell infiltration, upregulated the expression of GPX4 and SLC7A11. Further, it was demonstrated that HPWE treatment downregulated Nrf2 and its downstream target genes, i.e. HO-1 and NQO1 expression at the mRNA and protein levels. HPWE treatment also inhibited the activation of NF-κB p65 and downregulated its target genes, i.e. TNF-α and IL-1ß, expression. CONCLUSION: The present study showed that HPWE could relieve oxidative stress and ferroptosis via activating Nrf2 signaling pathway and inhibiting NF-κB mediated pathway.

Khasianine ameliorates psoriasis-like skin inflammation and represses TNF-α/NF-κB axis mediated transactivation of IL-17A and IL-33 in keratinocytes.

ETHNO-PHARMACOLOGICAL RELEVANCE: Khasianine is recently identified as a bioactive compound from Solanum nigrum L. (SNL) which is a traditional Chinese herb (named LongKui in China) and has been clinically applied for treating psoriasis in China but with limited knowledge about the active ingredients. AIM OF THE STUDY: This study tried to explore the bioactivity of Khasianine and showed that Khasianine possessed highly anti-inflammatory bioactivity which rapidly alleviated psoriasis-like mice skin inflammation. MATERIALS AND METHODS: Imiquimod induced psoriasis-like mouse model, and human keratinocytes were employed in this study. In vivo, immunohistochemistry and immunofluorescence were performed to evaluate the pathological improvement in psoriatic lesions after Khasianine treatment. In vitro, tumor necrosis factor α (TNF-α) treated HaCaT cells with or without Khasianine, were used to analyze the expression and cellular location of NF-κB p65, the expression of IL-17A and IL-33, and the binding intensity of NF-κB p65 on the promoter of IL-17A and IL-33 to understand the molecular mechanism of Khasianine mediated anti-inflammatory effect. RESULTS: Khasianine reduced infiltration of CD4+ T helper cells (Th cells) and macrophages in mice psoriatic lesions. Immunohistochemistry analysis revealed that Khasianine reduced TNF-α levels in lesions and suppressed NF-κB p65 activation as well as expression of IL-17A and IL-33 in mice epidermal keratinocytes. Further studies in human keratinocytes demonstrated that Khasianine inhibited TNF-α-induced transcriptional activation (transactivation) of NF-κB p65 such as evicting NF-κB p65 binding from the promoter regions of IL-17A and IL-33 and preventing NF-κB nuclear translocation. CONCLUSIONS: Our results suggested that Khasianine is a potent anti-inflammatory compound with the bioactivity of NF-κB inhibition and is a promising candidate for psoriasis topical therapy.

Ingredients with anti-inflammatory effect from medicine food homology plants.

Inflammation occurs when the immune system responses to external harmful stimuli and infection. Chronic inflammation induces various diseases. A variety of foods are prescribed in the traditional medicines of many countries all over the world, which gave birth to the concept of medicine food homology. Over the past few decades, a number of secondary metabolites from medicine food homology plants have been demonstrated to have anti-inflammatory effects. In the present review, the effects and mechanisms of the medicine food homology plants-derived active components on relieving inflammation and inflammation-mediated diseases were summarized and discussed. The information provided in this review is valuable to future studies on anti-inflammatory ingredients derived from medicine food homology plants as drugs or food supplements.

Efficacy and safety of Xiyanping injection in the treatment of COVID-19: A multicenter, prospective, open-label and randomized controlled trial.

Xiyanping (XYP) is a Chinese herbal medicine used in the clinic to treat respiratory infection and pneumonia. Recent evidence identified XYP as a potential inhibitor of severe acute respiratory syndrome coronavirus 2, implying XYP as a possible treatment for the coronavirus disease 2019 (COVID-19). Here, we conducted a prospective, multicenter, open-label and randomized controlled trial to evaluate the safety and effectiveness of XYP injection in patients with mild to moderate COVID-19. We consecutively recruited 130 COVID-19 patients with mild to moderate symptoms from five study sites, and randomized them in 1:1 ratio to receive XYP injection in combination with standard therapy or receive standard supportive therapy alone. We found that XYP injection significantly reduced the time to cough relief, fever resolution and virus clearance. Less patients receiving XYP injection experienced disease progression to the severe stage during the treatment process. No severe adverse events were reported during the study. Taken together, XYP injection is safe and effective in improving the recovery of patients with mild to moderate COVID-19. However, further studies are warranted to evaluate the efficacy of XYP in an expanded cohort comprising COVID-19 patients at different disease stages.

Chemical constituents from the rhizome of Polygonum paleaceum and their antifungal activity.

A new compounds neopaleaceolactoside (1), along with nine known compounds phyllocoumarin (2), quercetin (3), quercitrin (4), quercetin-3-methyl ether (5), vincetoxicoside B (6), isoquercitrin (7), kaempferol (8), (-)-epicatechin (9), and chlorogenic acid (10), was isolated from Polygonum paleaceum Wall. Their chemical structures were established based on one-dimensional and two-dimensional nuclear magnetic resonance techniques, mass spectrometry and by comparison with spectroscopic data reported. Some selected compounds were screened for their antifungal activity. Quercetin (3), vincetoxicoside B (6), kaempferol (8), and (-)-epicatechin (9) showed synergistic antifungal activities with the FICI values <0.5. A preliminary structure-activity relationship could be observed that free 3-OH in the structure of flavonoids was important for synergistic antifungal activity.

[Chemical Constituents from Polygonum paleaceum].

Objective: To isolate and identify the chemical constituents from Polygonum paleaceum. Methods: Chemical constituents were isolated and purified by column chromatography on silica gel,Sephadex HL-20 and macroporous resin etc. The chemical structures were identified by MS,NMR and spectral analysis. Results: Ten compounds were isolated and their structures were elucidated as ethyl chlorogenate( 1),methyl chlorogenate( 2), kaempferol-3-O-α-L-rhamnopyranoside( 3), (-)-epicatechin( 4), paleaceolactoside( 5), protocatechuic acid( 6), kaempferol( 7), gallic acid( 8), chlorogenic acid( 9) and isoquercitrin( 10). Conclusion: Compounds 1,3,6,7 and 10 are isolated from this plant for the first time.

Rhizoma Paridis Saponins Induces Cell Cycle Arrest and Apoptosis in Non-Small Cell Lung Carcinoma A549 Cells.

BACKGROUND: As a traditional Chinese medicine herb, Chonglou (Paris polyphylla var. chensiins) has been used as anticancer medicine in China in recent decades, as it can induce cell cycle arrest and apoptosis in numerous cancer cells. The saponins extract from the rhizoma of Chonglou [Rhizoma Paridis saponins (RPS)] is known as the main active component for anticancer treatment. However, the molecular mechanism of the anticancer effect of RPS is unknown. MATERIAL AND METHODS: The present study evaluated the effect of RPS in non-small-cell lung cancer (NSCLC) A549 cells using the 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry. Subsequently, the expression of several genes associated with cell cycle and apoptosis were detected by reverse transcription-quantitative polymerase chain reaction (qRT-PCR) and Western blotting. RESULTS: RPS was revealed to inhibit cell growth, causing a number of cells to accumulate in the G 1 phase of the cell cycle, leading to apoptosis. In addition, the effect was dose-dependent. Moreover, the results of qRT-PCR and Western blotting showed that p53 and cyclin-dependent kinase 2 (CDK2) were significantly downregulated, and that BCL2, BAX, and p21 were upregulated, by RPS treatment. CONCLUSIONS: We speculated that the RPS could act on a pathway, including p53, p21, BCL2, BAX, and CDK2, and results in G1 cell cycle arrest and apoptosis in NSCLC cells.