Indigodole E from Strobilanthes cusia exhibits anti-IL-17A effect.

One new indazole alkaloid, indigodole E (1), was isolated from a traditional Chinese medicine Qing Dai prepared from the aerial parts of Strobilanthes cusia. The structure of 1 was elucidated by NMR, MS, UV, and IR spectra as well as optical rotation. Additionally, compound 1 could obviously inhibit not only IL-17A protein production at concentrations from 1.25 to 2.5 µg/mL, but also IL-17 gene expression at concentrations from 5.0 to 10.0 µg/mL without cytotoxicity toward Th17 and Jukat cells, respectively. Overall, indazole analogue 1 could be the anti-IL 17 A contributor of Qing Dai in this investigation.

Optimal timing and effect of music therapy in patients with burn injuries: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Burn injuries may have both physiological and psychological consequences. Numerous studies have reported the use of music therapy during burn injury treatment, but the optimal timing for music therapy remains unclear. Therefore, we performed a systematic review and meta-analysis of randomized controlled trials on patients with burn injuries to analyze the effects of music intervention on them at different timings: background (T0) and time before (T1), during (T2), and after (T3) change dressing (CD). METHOD: The PubMed and EMBASE databases were searched for articles published before Novenber 2020 based on predetermined criteria. Our search focused on two keywords: music and burn. Reviewers extracted data from all eligible studies independently. The I2 statistic was used to determine statistical heterogeneity. The endpoints included standardized mean differences (SMDs) and 95% confidence intervals (CIs). Relevant Forest plots were also created. RESULT: This study finally included seven trials recruiting a total of 524 patients. The results indicated that compared with non-music intervention, music intervention significantly reduced anxiety at T0 (SMD = -1.32, 95% CI [-2.61, -0.02], T1 (SMD = -2.15, 95% CI [-4.30, -0.00]) and T2 (SMD = -0.39, 95% CI [-0.74, -0.04]). Moreover, they also significantly reduced the pain levels at T0 (SMD = -1.59, 95% CI [-2.00, -1.17]) and T2 (SMD = -0.47, 95% CI [-0.82, -0.12]), improved the mental condition, and reduced the amount of opioid analgesics used at T0. CONCLUSION: Music therapy seems to have some effects at T0 and T1 in patients with burn injuries. Music therapy was more effective in improving psychological outcomes than physiological outcomes. However, additional high-quality studies related to music therapy for patients with burn injuries are warranted.

Tuliposides H-J and Bioactive Components from the Bulb of Amana edulis.

Three new tuliposides H-J (1-3) and 11 known compounds were obtained from the methanolic extracts of the bulbs of Amana edulis for the first time. Their structures were elucidated by NMR, MS, and IR spectroscopic data, optical rotation, and Mosher's method. The melanogenesis properties of all the isolates were evaluated in B16 melanoma cells. Consequently, tributyl citrate (9) had anti-melanogenesis activity but was cytotoxic toward B16. (+)-Pyroglutamic acid (4), (+)-butyl 5-oxopyrrolidine-2-carboxylate (6), (-)-3-hydroxy-2-methylbutyrolactone (10), and 5-(hydroxymethyl)furfural (12) had increased melanin productions and tyrosinase activities. Those active components could be further studied as the candidates against melanoma and vitiligo for skin diseases or whitening/hypopigmentation for hair.

Characterization Of Secondary Metabolites From The Rhizome Of Cynara Scolymus And Their Antioxidant Properties.

The aerial portions of Cynara scolymus commonly have been eaten as vegetables or functional foods by the people lived in Mediterranean region. In preliminary antioxidant screening, the rhizome portions (CSR) of this species showed better potential than leaves ones. However, neither phytochemical nor pharmacology studies of CSR have been reported to date. The purpose of this research was to identify the active components from CSR through bioassay-guided fractionation. The antioxidant properties of secondary metabolites 1-9 were evaluated in this investigation. Compounds 4-6, 8, and 9 showed antioxidant activities based on DPPH free radical scavenging activity with IC50 values of 22.91-147.21 µM. Besides, compound 8 significantly and dose-dependently reduced H2O2-induced ROS levels in keratinocyte HaCaT cells without cytotoxicity toward HaCaT. Overall, our studies demonstrated the rhizome of C. scolymus could be used as a new natural antioxidant like the edible aerial portions and phenolic compounds are the active components.

IL-17A inhibitions of indole alkaloids from traditional Chinese medicine Qing Dai.

ETHNOPHARMACOLOGICAL RELEVANCE: Qing Dai, a famous traditional Chinese medicine (TCM), is prepared by a traditional fermentation process with the aerial part of Strobilanthes cusia. Currently, this TCM could treat various clinical inflammatory diseases, such as ulcerative colitis and psoriasis, however, the bioactive components of Qing Dai are unknown clearly. AIM OF THE STUDY: To isolate and identify the anti-IL-17A components of Qing Dai. MATERIALS AND METHODS: Silica, RP-18 gels, and size exclusion resin were used for column chromatography to isolate the pure compounds. The structures of isolates were elucidated by NMR, MS, UV, IR spectra, and optical rotation. IL-17A protein and gene expressions were also evaluated in the Th17 cell model and luciferase reporter assay, respectively. RESULTS: Two indole alkaloids, including one new indigodole D and cephalandole B, were isolated from Qing Dai. Indigodole D could inhibit IL-17A protein production during the Th17 polarization (EC50: 2.16 µg/mL) or after the polarization (EC50: 5.99 µg/mL) without cytotoxicity toward Th17 cells. Cephalandole B did not inhibit the IL-17A protein secretion. Nevertheless, both isolates notably inhibited IL-17A gene expression, especially cephalandole B, in a dose-dependent manner in Jukat cells with IL-17A luciferase reporter. CONCLUSIONS: Indole alkaloids, indigodoles A, C, D, tryptanthrin, and indirubin could contribute to anti-IL 17A properties of Qing Dai. The possible biogenetic mechanisms of above-mentioned indoles were also speculated in this investigation for further promising anti-IL-17 lead drugs development.

Antiviral Action of Tryptanthrin Isolated from Strobilanthes cusia Leaf against Human Coronavirus NL63.

Strobilanthes cusia (Nees) Kuntze is a Chinese herbal medicine used in the treatment of respiratory virus infections. The methanol extract of S. cusia leaf contains chemical components such as ß-sitosterol, indirubin, tryptanthrin, betulin, indigodole A, and indigodole B that have diverse biological activities. However, the antiviral action of S. cusia leaf and its components against human coronavirus remains to be elucidated. Human coronavirus NL63 infection is frequent among immunocompromised individuals, young children, and in the elderly. This study investigated the anti-Human coronavirus NL63 (HCoV-NL63) activity of the methanol extract of S. cusia leaf and its major components. The methanol extract of S. cusia leaf effectively inhibited the cytopathic effect (CPE) and virus yield (IC50 = 0.64 µg/mL) in HCoV-NL63-infected cells. Moreover, this extract potently inhibited the HCoV-NL63 infection in a concentration-dependent manner. Among the six components identified in the methanol extract of S. cusia leaf, tryptanthrin and indigodole B (5aR-ethyltryptanthrin) exhibited potent antiviral activity in reducing the CPE and progeny virus production. The IC50 values against virus yield were 1.52 µM and 2.60 µM for tryptanthrin and indigodole B, respectively. Different modes of time-of-addition/removal assay indicated that tryptanthrin prevented the early and late stages of HCoV-NL63 replication, particularly by blocking viral RNA genome synthesis and papain-like protease 2 activity. Notably, tryptanthrin (IC50 = 0.06 µM) and indigodole B (IC50 = 2.09 µM) exhibited strong virucidal activity as well. This study identified tryptanthrin as the key active component of S. cusia leaf methanol extract that acted against HCoV-NL63 in a cell-type independent manner. The results specify that tryptanthrin possesses antiviral potential against HCoV-NL63 infection.

Indole alkaloids indigodoles A-C from aerial parts of Strobilanthes cusia in the traditional Chinese medicine Qing Dai have anti-IL-17 properties.

Qing Dai (Naturalis Indigo) is a traditional Chinese medicine (TCM) used as a topical agent in moderate psoriasis, targeting interleukin-17 (IL-17). In this study, it was prepared from the aerial parts of Strobilanthes cusia. Three undescribed indole alkaloid derivatives, indigodoles A-C, along with seven known compounds were isolated from this preparation of Qing Dai and their structures were elucidated from spectroscopic data, including NMR, MS, UV, IR, optical rotation, and CD. As well, most compounds were tested against IL-17. Indigodole C and tryptanthrin could significantly inhibit IL-17 production of Th17 cells. In addition, indigodole A and indirubin showed notably anti-IL-17 gene expression in dose-dependent effects without cytotoxicities toward Th17 and Jurkat cells, respectively. Overall, our studies indicate that the aforementioned indole alkaloids could contribute to anti-IL 17 properties of Qing Dai.

New diterpenes leojaponins G-L from Leonurus japonicus.

Six new diterpenes, leojaponins G-L (1-6) along with 19 known compounds (7-25) were isolated from Leonurus japonicus. Their structures were elucidated by NMR, MS, IR, UV, and ECD spectroscopic data. Anti-melanogenesis assay indicated that 7 could safely and dose-dependently decrease melanin production in B16F10 melanoma cell with an IC50 value of 59.1 µM, but moderately inhibit tyrosinase activity. Without cytotoxicities at 20 µM, compounds 11, 14, 15, and 17-21 showed significant melanogenesis stimulation activities at the percentages of 7.7-48.2. Antioxidants 19 and 24 could notably inhibit ROS production in a dose-dependent manner with percentages of 24.7-42.2 and 27.9-40.2, respectively among the concentrations of 0.16 to 100 µM. Our results demonstrated L. japonicus and its constituents could be potential botanical resources of cosmeceutical development for treatment and prevention of skin disorders.

Changes in serum α-fetoprotein level predicts treatment response and survival in hepatocellular carcinoma patients and literature review.

BACKGROUND: Oxaliplatin-based chemotherapy is an alternative systemic treatment for patients with metastatic hepatocellular carcinoma (HCC) who were refractory or intolerant to sorafenib. To date, there have been no biomarkers reported to monitor the therapeutic efficacy and to predict the outcomes of HCC patients receiving oxaliplatin-based chemotherapy. METHODS: Eighty-one HCC patients with elevated baseline α-fetoprotein (AFP) levels and extrahepatic spreading who received oxaliplatin-based chemotherapy between 2012 and 2014 were retrospectively enrolled in this study. Two AFP tests were performed, at baseline and 2-4 weeks after the initiation of chemotherapy. The change in AFP levels was calculated for survival analysis. RESULTS: In the AFP decline group (decreased compared to baseline), the median progression-free survival (PFS) and overall survival (OS) were 7.0 months and 12.3 months, respectively. In the AFP nondecline group, the median PFS and OS were 2.3 months and 3.0 months, respectively. The difference in OS between the two groups was significant (p < 0.005). In the multivariate analysis for disease progression, the best response to chemotherapy and AFP decline were independent factors, with p values of 0.004 and 0.009, respectively. In the multivariate analysis for OS, the baseline Child-Pugh score, best response to chemotherapy, and AFP decline were independent prognostic factors, with p values of 0.01, 0.001, and 0.008, respectively. Additionally, the unit change in AFP level was predictive of PFS and OS with p values of 0.007 and 0.001, respectively. CONCLUSION: The change in AFP levels 2-4 weeks after initiating oxaliplatin-based chemotherapy is useful to predict treatment response and survival.

Characterization of Secondary Metabolites from Purple Ipomoea batatas Leaves and Their Effects on Glucose Uptake.

Ipomoea batatas has long been used in folk medicine for the treatment of hyperglycemia or as a food additive for the prevention of type 2 diabetes. However, neither the plant extract nor its active components have been evaluated systematically. In this work four crude extracts, including n-hexane- (IBH), 95% MeOH- (IBM), n-BuOH- (IBB), and H2O-soluble (IBW) fractions, were prepared by fractionation of a methanolic extract of purple I. batatas leaves. Twenty-four pure compounds 1-24 were then isolated by various chromatographic techniques and their structures identified from NMR and MS data. Glucose uptake assays in differentiated 3T3-L1 adipocytes and rat primary hepatocytes, as well as western blot analysis, were carried out to evaluate the antidiabetic activity of this species. The IBH crude fraction, with methyl decanoate (22) as a major and active compound, showed the greatest effect on glucose uptake, most likely via activation of Glut4 and regulation of the PI3K/AKT pathway. Quercetin 3-O-ß-d-sophoroside (1), quercetin (3), benzyl ß-d-glucoside (10), 4-hydroxy-3-methoxybenzaldehyde (12), and methyl decanoate (22) could be important components contributing to the antidiabetic effects. We conclude that purple I. batatas leaves have potential as an antidiabetic plant source and the active constituents 1, 3, 10, 12, and 22 are promising lead candidates for future investigation.

The Roles of 4ß-Hydroxywithanolide E from Physalis peruviana on the Nrf2-Anti-Oxidant System and the Cell Cycle in Breast Cancer Cells.

4[Formula: see text]-Hydroxywithanolide E is an active component of the extract of Physalis peruviana that has been reported to exhibit antitumor effects. Although the involvement of reactive oxygen species (ROS) production and the ataxia-telangiectasia mutated protein (ATM)-dependent DNA damage signaling pathway in 4[Formula: see text]-hydroxywithanolide E-induced apoptosis of breast cancer MCF-7 cells was demonstrated in our previous study, the relationship between ROS production and the cellular defense system response in 4[Formula: see text]-hydroxywithanolide E-induced cell death requires further verification. The present study suggests that ROS play an important role in 4[Formula: see text]-hydroxywithanolide E-induced MCF-7 cell death in which anti-oxidants, such as glutathione or N-acetylcysteine, can resist the 4[Formula: see text]-hydroxywithanolide E-induced accumulation of ROS and cell death. Furthermore, N-acetylcysteine or glutathione can reverse the 4[Formula: see text]-hydroxywithanolide E-induced changes in the cell cycle distribution and the expression of cell cycle regulators. We found that the 4[Formula: see text]-hydroxywithanolide E-induced ROS accumulation was correlated with the upregulation of Nrf2 and Nrf2-downstream genes, such as antioxidative defense enzymes. In general, the activity of Nrf2 is regulated by the Ras signalling pathway. However, we demonstrated that Nrf2 was activated during 4[Formula: see text]-hydroxywithanolide E-induced MCF-7 cell death in spite of the 4[Formula: see text]-hydroxywithanolide E-induced inhibition of the Ras/Raf/ERK pathway. The activity and protein expression of superoxide dismutase and catalase were involved in the 4[Formula: see text]-hydroxywithanolide E-induced ROS production in MCF-7 cells. Furthermore, 4[Formula: see text]-hydroxywithanolide E was demonstrated to significantly reduce the sizes of the tumor nodules in the human breast cancer MDA-MB231 xenograft tumor model.

Anti-inflammatory Cerebrosides from Cultivated Cordyceps militaris.

Cordyceps militaris (bei-chong-chaw, northern worm grass) is a precious and edible entomopathogenic fungus, which is widely used in traditional Chinese medicine (TCM) as a general booster for the nervous system, metabolism, and immunity. Saccharides, nucleosides, mannitol, and sterols were isolated from this fungus. The biological activity of C. militaris was attributed to the saccharide and nucleoside contents. In this study, the aqueous methanolic fraction of C. militaris fruiting bodies exhibited a significant anti-inflammatory activity. Bioactivity-guided fractionation of the active fraction led to the isolation of eight compounds, including one new and two known cerebrosides (ceramide derivatives), two nucleosides, and three sterols. Cordycerebroside A (1), the new cerebroside, along with soyacerebroside I (2) and glucocerebroside (3) inhibited the accumulation of pro-inflammatory iNOS protein and reduced the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophages. This is the first study on the isolation of cerebrosides with anti-inflammatory activity from this TCM.

Anti-inflammatory and cytotoxic compounds from Solanum macaonense.

One new cerebroside, macaocerebroside A (1), and 15 known compounds (2-16) were isolated from Solanum macaonense for the first time. In an antineutrophilic inflammatory assay, four caffeic acid derivatives (2-5) were active against superoxide anion generation with IC50 values of 3.3-4.8 µM; especially, 3 inhibited elastase release with an IC50 value of 4.0 µM. Additionally, kaempferol (8) also showed inhibition against elastase release with an IC50 value of 4.0 µM. In a cytotoxic assay, rutin (14) had selective moderate cytotoxicity toward human lung (A549), bladder (NTUB1), and prostate (DU145) cancer cell lines with IC50 values of 34.6, 41.3, and 31.8 µM, respectively.

Anti-Inflammatory Spirostanol and Furostanol Saponins from Solanum macaonense.

Eight new spirostanol saponins, macaosides A-H (1-8), and 10 new furostanol saponins, macaosides I-R (9-18), together with six known spirostanol compounds (19-24) were isolated from Solanum macaonense. The structures of the new compounds were determined from their spectroscopic data, and the compounds were tested for in vitro antineutrophilic inflammatory activity. It was found that both immediate inflammation responses including superoxide anion generation and elastase release were significantly inhibited by treatment with compounds 20, 21, and 24 (superoxide anion generation: IC50 7.0, 7.6, 4.0 µM; elastase release: IC50 3.7, 4.4, 1.0 µM, respectively). However, compounds 1 and 4 exhibited effects on the inhibition of elastase release only, with IC50 values of 3.2 and 4.2 µM, respectively, while 19 was active against superoxide anion generation only, with an IC50 value of 6.1 µM. Accordingly, spirostanols may be promising lead compounds for further neutrophilic inflammatory disease studies.

Antiplatelet aggregation effects of phenanthrenes from Calanthe arisanensis.

Three phenanthrenes (1-3), four indole alkaloids (4-7) and one steroid (8) were isolated from the leaves of Calanthe arisanensis for the first time. In the antiplatelet aggregation assay, phenanthrenes 1 and 2 showed potential antiplatelet activity. We have reported and discussed here the antiplatelet aggregation properties of the eleven naturally-occurring phenanthrenes (1-2 and 9-17) isolated from the underground part of the plant and eighteen chemically synthesized phenanthrenes (18-35). Overall, our data demonstrated that 1,4-phenanthrenequinones 20, 21 and 22 (collagen, IC50 0.2, 0.2, 0.1 microg/mL; thrombin, IC50 0.8, 1.0, 1.1 microg/mL, respectively) could be promising lead candidates for further cardiovascular disease studies.

Anti-neutrophilic inflammatory steroidal glycosides from Solanum torvum.

Torvpregnanosides A and B, two pregnane glycosides, and torvoside Q, a 23-keto-spirostanol glycoside, along with twelve known steroidal saponins were isolated from aerial parts of Solanum torvum. Of the latter, four of the 23-hydroxy-spirostanol glycosides, and, a yamogenin glycoside, were in this plant discovered. All structures were identified from spectroscopic data, and all the compounds were tested for in vitro anti-neutrophilic inflammatory activity. Two compounds showed selective inhibition against elastase release and superoxide anion generation, respectively, by human neutrophils with IC50 values of 5.66 and 3.59 µM, while two others inhibited both inflammatory mediators with IC50 values of 0.66-3.49 µM. Structure-activity relationships are discussed.

Traditional Chinese Medicine ZHENG Identification Provides a Novel Stratification Approach in Patients with Allergic Rhinitis.

Background. We aimed to apply the ZHENG identification to provide an easy and useful tool to stratify the patients with allergic rhinitis (AR) through exploring the correlation between the quantified scores of AR symptoms and the TCM ZHENGs. Methods. A total of 114 AR patients were enrolled in this observational study. All participants received the examinations of anterior rhinoscopy and acoustic rhinometry. Their blood samples were collected for measurement of total serum immunoglobulin E (IgE), blood eosinophil count (Eos), and serum eosinophil cationic protein (ECP). They also received two questionnaire to assess the severity scores of AR symptoms and quantified TCM ZHENG scores. Multiple linear regression analysis was used to determine explanatory factors for the score of AR manifestations. Results. IgE and ECP level, duration of AR, the 2 derived TCMZHENG scores of "Yin-Xu - Yang-Xu", and "Qi-Xu + Blood-Xu" were 5 explanatory variables to predict the severity scores of AR symptoms. The patients who had higher scores of "Yin-Xu - Yang-Xu" or "Qi-Xu + Blood-Xu" tended to manifest as "sneezer and runner" or "blockers," respectively. Conclusions. The TCM ZHENG scores correlated with the severity scores of AR symptoms and provided an easy and useful tool to stratify the AR patients.

Indiosides G-K: steroidal glycosides with cytotoxic and anti-inflammatory activities from Solanum violaceum.

Five new steroidal glycosides (1-5) and nine known compounds were isolated from Solanum violaceum. Indiosides G (1) and H (2) are spirostene saponins with an iso-type F ring, indioside I (3) is a spirostane saponin, and indiosides J (4) and K (5) are unusual furostanol saponins with a deformed F ring. These structures represent rare naturally occurring steroidal skeletons. The structures of the new compounds were elucidated using 1D and 2D spectroscopic techniques and acid hydrolysis. Compounds 2, 3, and 7-9 exhibited cytotoxic activity against six human cancer cell lines (HepG2, Hep3B, A549, Ca9-22, MDA-MB-231, and MCF-7) with IC(50) values of 1.83-8.04 µg/mL. Steroidal saponins 3, 8, and 9 showed inhibitory effects on superoxide anion generation with IC(50) values of 2.84 ± 0.18, 0.62 ± 0.03, and 1.62 ± 0.59 µg/mL, respectively. Saponins 8 and 9 also inhibited elastase release with IC(50) values of 111.05 ± 7.37 and 4.04 ± 0.51 µg/mL, respectively. Structure-activity relationship correlations of these compounds with respect to cytotoxic and anti-inflammatory effects are discussed.

Anti-neutrophilic inflammatory secondary metabolites from the traditional Chinese medicine, Tiankuizi.

Through bioassay-guided fractionation, thirteen compounds (1-13) were isolated from the dry root of Semiaquilegia adoxoides, known as Tiankuizi in traditional Chinese medicine (TCM). Among these, four benzoic acid derivatives (1, 2, 4, 5), one 4,6-dimethoxy-5-methyl-2H-pyran-2-one (10) and one 1,2,3-propanetriol (13) were found for the first time in S. adoxoides. This is the first record of compound 10 from a natural source. 4-Hydroxybenzoic acid (1) and 3,4-dihyroxybenzoic acid (2) showed selective inhibition against elastase release and superoxide anion generation, with IC50 values of 3.20 and 6.21 microg/mL, respectively. Compound 1 had 7-fold better activity than the positive control against elastase release induced by human neutrophils. Overall, our studies demonstrated Tiankuizi (S. adoxoides) as a potential TCM and isolates 1 and 2 as promising lead compounds for neutrophilic inflammatory diseases.

Antioxidant and tyrosinase inhibitory constituents from a desugared sugar cane extract, a byproduct of sugar production.

Recycling agricultural resources has become an important issue worldwide promoting the economical value of agricultural production processes. Desugared sugar cane extract (DSE) from Saccharum officinarum is a byproduct obtained during sugar production. Two new neolignan glucosides, saccharnan A (1) and saccharnan B (2), together with 10 known phenolics (3-12) were isolated from DSE, and their structures were elucidated on the basis of NMR spectral analysis. Compounds 3, 4, 8, and 9 showed good activity against DPPH radical (IC(50) ≤ 51.20 µM) and compounds 3-8 and 12 exhibited strong ABTS(+) free radical scavenging activity (IC(50) ≤ 51.57 µM) compared to those of the positive controls, ascorbic acid and Trolox. Moreover, compounds 7 and 12 acted as potent tyrosinase inhibitors (IC(50) ≤ 42.59 µM) compared to the positive control arbutin. Our results highlighted the economical value of recycling DSE for the future development of natural antioxidants and/or tyrosinase inhibitors.