The gut microbe-derived metabolite trimethylamine-N-oxide induces aortic valve fibrosis via PERK/ATF-4 and IRE-1α/XBP-1s signaling in vitro and in vivo.

BACKGROUND AND AIMS: The gut microbe-derived metabolite trimethylamine-N-oxide (TMAO) has been implicated in the development of cardiovascular fibrosis. Endoplasmic reticulum (ER) stress occurs after the dysfunction of ER and its structure. The three signals PERK/ATF-4, IRE-1α/XBP-1s and ATF6 are activated upon ER stress. Recent reports have suggested that the activation of PERK/ATF-4 and IRE-1α/XBP-1s signaling contributes to cardiovascular fibrosis. However, whether TMAO mediates aortic valve fibrosis by activating PERK/ATF-4 and IRE-1α/XBP-1s signaling remains unclear. METHODS: Human aortic valve interstitial cells (AVICs) were isolated from aortic valve leaflets. PERK IRE-1α, ATF-4, XBP-1s and CHOP expression, and production of collagen Ⅰ and TGF-ß1 were analyzed following treatment with TMAO. The role of PERK/ATF-4 and IRE-1α/XBP-1s signaling pathways in TMAO-induced fibrotic formation was determined using inhibitors and small interfering RNA. RESULTS: Diseased valves produced greater levels of ATF-4, XBP-1, collagen Ⅰ and TGF-ß1. Interestingly, diseased cells exhibited augmented PERK/ATF-4 and IRE-1α/XBP-1s activation after TMAO stimulation. Inhibition and silencing of PERK/ATF-4 and IRE-1α/XBP-1s each resulted in enhanced suppression of TMAO-induced fibrogenic activity in diseased cells. Mice treated with dietary choline supplementation had substantially increased TMAO levels and aortic valve fibrosis, which were reduced by 3,3-dimethyl-1-butanol (DMB, an inhibitor of trimethylamine formation) treatment. Moreover, a high-choline and high-fat diet remodeled the gut microbiota in mice. CONCLUSIONS: TMAO promoted aortic valve fibrosis through activation of PERK/ATF-4 and IRE-1α/XBP-1s signaling pathways in vitro and in vivo. Modulation of diet, gut microbiota, TMAO, PERK/ATF-4 and IRE1-α/XBP-1s may be a promising approach to prevent aortic valve fibrosis.

Serum Klotho Modifies the Associations of 25-Hydroxy Vitamin D With All-Cause and Cardiovascular Mortality.

BACKGROUND: The association between 25-hydroxyvitamin D and mortality remains controversial. Klotho, a biomarker of vitamin D activation and metabolism, may play a key role in this association. However, it is unclear whether the association between vitamin D deficiency and mortality risk is modified by klotho levels. Therefore, this study investigated the joint association of serum 25-hydroxyvitamin D [25(OH)D] and klotho with mortality risk in American community-dwelling adults. METHODS: A total of 9870 adults from the National Health and Nutrition Examination Survey (2007-2016) were included in our study. Mortality data were ascertained by linking participants to National Death Index records. Cox proportional hazards models were used to assess the association among serum 25(OH)D, serum klotho, and all-cause and cardiovascular disease (CVD) mortality. RESULTS: We found a significant interaction between klotho and serum 25(OH)D in all-cause mortality (P = .028). With klotho > 848.4 pg/mL (risk threshold on mortality), no significant all-cause and CVD mortality risk was observed at any level of serum 25(OH)D. However, with klotho < 848.4 pg/mL, a significant all-cause and CVD mortality risk was observed with serum 25(OH)D < 50 nmol/L [hazards ratio (HR), 1.36; 95% confidence interval (CI), 1.10-1.69; HR, 1.78; 95% CI, 1.16-3.45) and serum 25(OH)D of continuous variable (HR, 0.98; 95% CI, .97-.99; HR, 0.98; 95% CI, .98-.99). In addition, vitamin D metabolism disruption accessed by the combination of decreasing serum 25(OH)D (<50 nmol/L) and klotho (<848.4 pg/mL) was associated with significant all-cause mortality (HR, 1.48; 95% CI, 1.11-1.96) and CVD mortality (HR, 2.36; 95% CI, 1.48-3.75). CONCLUSIONS: Vitamin D-associated mortality risk is observed only with concurrently decreasing klotho, indicating that vitamin D metabolism dysfunction increases the risk of mortality. Klotho levels could help predict long-term mortality outcomes and thus may be useful concurrently for guiding vitamin D supplementation therapy decision-making in populations with vitamin D deficiency.

Quality control for a traditional Chinese medicine, Millettia speciosa Champ, using ultra-high-performance liquid chromatography fingerprint, serum pharmacochemistry and network pharmacology.

Millettia speciosa (M. speciosa) Champ (MSC) is a healthy food type with medicinal and edible homology, which is now considered a clinically significant anti-rheumatoid arthritis medicine. However, there is currently no standardized or generally accepted research strategy by which we can assess M. speciosa. Thus, it is essential to develop novel theories, strategies and evaluation methods for the scientific quality control of M. speciosa. Herein, our use ultra-high-performance liquid chromatography (UPLC)-MS/MS analysis identified 12 common bioactive components absorbed into MSC serum. Next, network pharmacology analysis exhibited that 5 MSC components may be those active components in treating rheumatoid arthritis and may be considered potential quality markers. These 5 components were then quantified using a fast UPLC approach, based on the quality marker of measurability, showing that lenticin can be regarded as the MSC quality marker. The cumulative study findings, based on systematic assessment of chemical composition both in vivo and in vitro, and the potential efficacy of M. speciosa, provide a novel approach for M. speciosa quality control.

Dietary Zinc Supplemented in Organic Form Affects the Expression of Inflammatory Molecules in Swine Intestine.

Animals receiving Zinc (Zn) dietary supplementation with organic sources respond better to stress than inorganic Zn sources supplementation. The study aimed to identify the effect of different Zn sources on intestinal epithelial gene expression. In total, 45 pigs (9 per treatment) (77.5 ± 2.5 kg weight) were fed for 32 days, a corn-soybean meal diet without supplemented Zn (ZnR) or supplemented with 50 and 100 ppm of inorganic ZnCl2 (Zn50 and Zn100), and amino acid-bound organic Zn sources (LQ50 and LQ100). Gene expression changes form RNA-seq in ileum tissues of ZnR revealed changes associated with Zn insufficiency. Comparing organic with inorganic Zn sources by one-way ANOVA, pro-inflammatory cytokine interleukin 18 (IL18) was downregulated (p = 0.03) and Toll-like receptor 2 (TLR2) upregulated (p = 0.02). To determine the role of epithelial cells in response to dietary Zn, swine intestinal organoids (enteroids) were exposed to Zn restriction, ZnCl2 or LQ-Zn. In enteroids, ZIP4 expression decreased with added Zn compared with Zn-restriction (p = 0.006) but Zn sources did not affect (p > 0.05) IL18 or TLR2 expression. These results suggest that organic Zn may stimulate TLR2 signaling possibly affecting immune response, while decreasing the proinflammatory cytokine IL18 expression in non-epithelial cells of intestinal mucosa.

Vicatia thibetica de Boiss: Botany, Traditional Uses, Phytochemistry, Quantitative Analysis, and Pharmacology.

BACKGROUND: Vicatia thibetica de Boiss is a common Tibetan medicine used for both medicine and food, belonging to the family Apiaceae. This plant has the functions of dispelling wind, removing dampness, dispersing cold, and relieving pain. It has great development potential and application prospects in food development and medicinal value. METHODS: The related references on botany, traditional uses, phytochemistry, quantitative analysis, and pharmacology of V. thibetica de Boiss had been retrieved from both online and offline databases, including PubMed, ScienceDirect, Web of Science, Elsevier, Willy, SpringLink, SciFinder, Google Scholar, Baidu Scholar, ACS publications, SciHub, Scopus, and CNKI. RESULTS: V. thibetica de Boiss exerts nourishing, appetizing, and digestive effects according to the theory of Tibetan medicine. Phytochemical reports have revealed that V. thibetica de Boiss contains flavonoids, coumarins, sterols, and organic acids. Meanwhile, the quantitative analysis of the chemical constituents of V. thibetica de Boiss has been done by means of UPLC-Q-TOF-MS. It has also been found that V. thibetica de Boiss possesses multiple pharmacological activities, including anti-fatigue, anti-oxidant, anti-aging, and non-toxic activities. CONCLUSION: This paper has comprehensively summarized botany, traditional uses, phytochemistry, quantitative analysis, and pharmacology of V. thibetica de Boiss. It will not only provide an important clue for further studying V. thibetica de Boiss, but also offer an important theoretical basis and valuable reference for in-depth research and exploitation of this plant in the future.

Recent advances of activation techniques-based discovery of new compounds from marine fungi.

Natural products have been playing an indispensable role in drug discovery. However, it seems that the golden period of discovering new compounds has passed since the first antibiotic-penicillin. With the development of genome sequencing, it has been found that marine fungi contain various biosynthetic gene clusters (BGCs), which are silent under standard laboratory conditions. Therefore, it might be envisioned that once these BGCs are expressed, a large quantity of new secondary metabolites with biological activities could be generated. This paper reviewed several activation techniques implemented from 2020 to 2022, including epigenetics regulation, co-culture, precursor feeding, heterologous expression, and changing fermentation parameters to activate silent BGCs of marine fungi. We also described the diversity and bioactivities of these newly discovered uncommon marine fungi-derived compounds based on the classification of activation techniques, facilitating research groups focusing on natural products to enhance discovering efficiency.

Shengji solution accelerates the wound angiogenesis of full-thickness skin defect in rats via activation of TGF-ß1/Smad3-VEGF signaling pathway.

Shengji solution is made according to the classic prescription - Shengji prescription. Shengji solution is a external prescription of traditional Chinese medicine with the functions of nourishing blood, relieving pain, producing muscle and shrinking the wound. In the present study, we investigated the therapeutic effects of Shengji solution on dorsal full-thickness skin defects in rats. We also detected the activation of transforming growth factor beta1 (TGF-ß1)/SMAD3/vascular endothelial growth factor (VEGF) signaling pathways in the wound-healing process. The results showed that the wound was cleaned with normal saline followed by bandaging with cotton gauze according to the groups, respectively: (a) control group; (b) Kangfuxin group, the wound was moistened with Kangfuxin solution; (c) Shengji solution group, the wounds were moistened with Shengji solution; (d) Shengji solution+SB431542 inhibitor group, the wound was moistened with Shengji solution, and then SB431542 inhibitor (10 mg/kg) was injected intraperitoneally for 5 days. On the 14th day after operation, the wound-healing rate of Shengji solution group was more than 95% and also greater than that in the control group and Shengji solution+SB431542 inhibitor group. Besides, Shengji solution could inhibit the inflammation and capillary production by enhancing the epithelial regeneration, dermal repair and angiogenesis. Moreover, Shengji solution could also increase CD34 content, the expressions of TGF-ß1, VEGF proteins and the phosphorylation of SMAD3 in wound granulation tissue. In conclusion, Shengji solution can accelerate the dermal cutaneous wound healing in rats, stimulate angiogenesis and collagen synthesis by activating TGF-ß1/SMAD3/VEGF pathway.

The activities and mechanisms of intestinal microbiota metabolites of TCM herbal ingredients could be illustrated by a strategy integrating spectrum-effects, network pharmacology, metabolomics and molecular docking analysis: Platycodin D as an example.

BACKGROUND: The intestinal microbiota plays a key role in understanding the mechanism of traditional Chinese medicine (TCM), as it could transform the herbal ingredients to metabolites with higher bioavailability and activity comparing to their prototypes. Nevertheless, the study of the activity and mechanism of microbiota metabolites reported by the published literature still lacks viable ways. Hence a new strategy is proposed to solve this issue. PURPOSE: A new strategy to study the activity and mechanism of intestinal microbiota metabolites of TCM herbal ingredients by integrating spectrum-effect relationship, network pharmacology, metabolomics analysis and molecular docking together was developed and proposed. METHOD: Platycodin D (PD) and its microbiota metabolites with antitussive and expectorant effect were selected as an example for demonstration. First, the PD and its microbiota metabolites with important contribution to antitussive and/or expectorant effects were screened through spectrum-effect relationship analysis. Second, network pharmacology and metabolomics analysis were integrated to identify the upstream key targets of PD and its microbiota metabolites as well as the downstream endogenous metabolites. Finally, the active forms of PD were further confirmed by molecular docking. RESULTS: Results showed that PD was an active ingredient with antitussive and/or expectorant effects, and the active forms of PD were its microbiota metabolites: 3-O-ß-d-glucopyranosyl platycodigenin, 3-O-ß-d-glucopyranosyl isoplatycodigenin, 7­hydroxyl-3-O-ß-d-glucopyranosyl platycodigenin, platycodigenin and isoplatycodigenin. In addition, those microbiota metabolites could bind the key targets of PAH, PLA2G2A, ALOX5, CYP2C9 and CYP2D6 to exert antitussive effects by regulating four metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, glycerophospholipid metabolism and linoleic acid metabolism. Similarly, they could also bind the key targets of PLA2G1B, ALOX5, CYP2C9 and CYP2D6 to exert expectorant effect by regulating two pathways of glycerophospholipid metabolism and linoleic acid metabolism. CONCLUSION: The proposed strategy paves a new way for the illustration of the activities and mechanisms of TCM herbal ingredients, which is very important to reconcile the conundrums of TCM herbal ingredients with low oral bioavailability but high activity.

Ethnopharmacology, Phytochemistry, and Pharmacology of Pyrethrum tatsienense (Bureau & Franch.) Ling ex C. Shih: A Comprehensive Review.

BACKGROUND: Pyrethrum tatsienense (Bureau & Franch.) Ling ex C. Shih (PTLCS) belongs to the family Compositae, which is a perennial medicinal plant mainly distributed in the Qinghai-Tibet Plateau of China. This review provides a comprehensive summary of the ethnopharmacology, phytochemistry, and pharmacology of PTLCS. This review offers valuable references and guidance for researching PTLCS in depth. METHODS: The related references of PTLCS were retrieved from an online database, such as Web of Science, Google Scholar, SciFinder, PubMed, SpringLink, Elsevier, Willy, CNKI, and so on. RESULTS: PTLCS is widely reported for treating headaches, head injuries, traumatic injuries, anabrosis, impetigo, hepatitis, and other diseases in the medical field. Phytochemical research revealed that this plant contained flavonoid aglycones, flavonoid glycosides, xanthones, triterpenoids, coumarins, polyacetylenes, volatile oils, and other compounds. Meanwhile, PTLCS exhibited extensive pharmacological activities including anti-cardiac ischemia, anti-hypoxia, hepatoprotective, anti- inflammatory and analgesic, and antioxidant activities. CONCLUSIONS: PTLCS is widely used as a Tibetan medicine, which has a variety of chemicals with diverse bioactivities. Therefore, further studies are necessary to perform on the PTLCS to assay biological activities, discover their bioactive constituents, and reveal pharmacological mechanisms. This review may supply an important theoretical basis and valuable reference for in-depth research and exploitations of PTLCS.

Ethnopharmacology, Phytochemistry, and Pharmacology of Highland Barley Monascus purpureus Went: A Comprehensive Review.

BACKGROUND: Highland barley Monascus purpureus Went, a traditional Tibetan medicine with food functions, which is fermented by Monascus purpureus with highland barley as substrate. It possesses various medical functions of promoting blood circulation and removing blood stasis, invigorating spleen and promoting digestion in folk of the Qinghai-Tibet Plateau in China. This review provides a comprehensive overview of ethnopharmacology, phytochemistry, and pharmacology of highland barley Monascus purpureus Went. METHODS: The references of highland barley Monascus purpureus Went were retrieved from the online database, such as Web of Science, Google Scholar, SciFinder, PubMed, SpringLink, Elsevier, Willy, CNKI, and so on. RESULTS: Phytochemical research revealed that highland barley Monascus purpureus Went contained multiple chemical components, including Monascus pigments, monacolins, lactones, and other compounds. The reported pharmacological activities of highland barley Monascus purpureus Went included hypolipidemic, anti-nonalcoholic fatty liver disease, and hepatoprotective activities. CONCLUSION: In a word, botany, ethnopharmacology, phytochemistry and pharmacology of highland barley Monascus purpureus Went were reviewed comprehensively in this paper. In the future, highland barley Monascus purpureus Went needs further study, such as paying more attention to quality control and utilization of medicine. Therefore, this review may provide a theoretical basis and valuable data for future studies and exploitations on highland barley Monascus purpureus Went.

[Mechanism of Danggui Sini Decoction in improving kidney injury caused by blood stasis syndrome based on metabolomics and network pharmacology].

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.

[Activity of Codonopsis canescens against rheumatoid arthritis based on TLRs/MAPKs/NF-κB signaling pathways and its mechanism].

This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1ß, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1ß, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.

Dietary zinc restriction affects the expression of genes related to immunity and stress response in the small intestine of pigs.

Zinc (Zn) is an essential mineral and its deficiency manifests in non-specific clinical signs that require long time to develop. The response of swine intestine to Zn restriction was evaluated to identify early changes that can be indicative of Zn deficiency. Twenty-seven pigs (body weight = 77⋅5 ± 2⋅5 kg) were assigned to one of three diets: diet without added Zn (Zn-restricted diet, ZnR), and ZnR-supplemented with either 50 (Zn50) or 100 mg of Zn/kg of diet (Zn100) of Zn supplied by ZnCl2. After 32 d consuming the diets, serum Zn concentration in ZnR pigs was below the range of 0⋅59-1⋅37 µg/ml considered sufficient, thereby confirming subclinical Zn deficiency. Pigs showed no obvious health or growth changes. RNA-seq analysis followed by qPCR showed decreased expression of metallothionein-1 (MT1) (P < 0⋅05) and increased expression of Zn transporter ZIP4 (P < 0⋅05) in jejunum and ileum of ZnR pigs compared with Zn-supplemented pigs. Ingenuity pathway analysis revealed that Zn50 and Zn100 induced changes in genes related to nucleotide excision repair and integrin signalling pathways. The top gene network in the ZnR group compared with Zn100 was related to lipid and drug metabolism; and compared with Zn50, was related to cellular proliferation, assembly and organisation. Dietary Zn concentrations resulted in differences in genes related to immune pathways. Our analysis showed that small intestine presents changes associated with Zn deficiency after 32 d of Zn restriction, suggesting that the intestine could be a sentinel organ for Zn deficiency.

Effects of qigong exercise on the physical and mental health of college students: a systematic review and Meta-analysis.

BACKGROUND: Physical and mental health problems are becoming more serious among college students due to lifestyle changes and increased academic stress. Qigong exercise has been regarded as a potentially effective intervention to improve the physical and mental health of college students. METHODS: Eleven databases were searched from their respective inception dates to April 2022. Relevant randomized controlled trials (RCTs) were included. Physical and psychological conditions, including limb muscle strength, flexibility, cardiorespiratory endurance, vital capacity, blood pressure and heart rate, as well as depression, anxiety and mood, were evaluated. The risk of bias was assessed with the Cochrane Collaboration tool. RESULTS: Sixteen randomized controlled trials were included in the meta-analysis. Significant improvements in cardiorespiratory endurance (MD = 3.83, 95% CI: 0.99 to 6.67, P = 0.008) and flexibility (MD = 3.01, 95% CI: 1.21 to 4.81, P = 0.001) were observed. We also observed that Qigong exercise significantly reduced depression and anxiety symptoms (SMD=-0.89, 95% CI: -1.17 to -0.61, P < 0.00001; SMD=-0.78, 95% CI: -1.31 to -0.25, P = 0.004). Nevertheless, no significant effects on muscle strength, vital capacity, blood pressure, heart rate or mood were found. CONCLUSION: Qigong exercise was advantageous for college students in terms of improving flexibility and cardiorespiratory endurance and alleviating depression and anxiety to some extent. However, due to the limited number of eligible trials and the low methodological quality, more well-designed RCTs are needed in the future.

Polyoxygenated cembranoids from the South China Sea soft coral Sarcophyton boettgeri and their stereochemistry.

Four new polyoxygenated cembranoids, namely sarcoboettgerol A (1), 12-epi-humilisin D (2), sarcoboettgerol B (3), and sarcoboettgerol C (4), together with one known related analogue, humilisin D (5), were isolated and characterized from the soft coral Sarcophyton boettgeri collected off Ximao island, Hainan Province, China. The structures and absolute configurations of the new compounds were determined by extensive spectroscopic data analyses, Cu kα single crystal X-ray diffraction analysis, and TDDFT-ECD calculations. A plausible biogenetic relationship of 3 and 4 was proposed.

Pulmonary delivery of liposomes co-loaded with SN38 prodrug and curcumin for the treatment of lung cancer.

A co-delivery system of SN38 (7-ethyl-10-hydroxyl camptothecin) prodrug and CUR (curcumin) was designed for the treatment of lung cancer by pulmonary delivery. SN38 was linked to cell-penetrating peptide (CPP) TAT via a polyethylene glycol (PEG) linker to form the SN38 prodrug (TAT-PEG-SN38). Liposomes co-loaded with amphiphilic TAT-PEG-SN38 and curcumin (Lip-TAT-PEG-SN38/CUR) were successfully prepared by a microfluidic method for the treatment of lung cancer via pulmonary delivery. Lip-TAT-PEG-SN38/CUR showed nanometer-sized sphericity and a particle size of 171.21 nm. Besides, Lip-TAT-PEG-SN38/CUR exhibited enhanced antiproliferative effect, increased cell apoptosis induction and improved cell cycle arrest compared to the single agents in vitro. The combination induced significant tumor inhibition in a BALB/c mouse lung cancer model. These results indicated that our SN38 prodrug and curcumin co-delivery system was a promising candidate for lung cancer treatment.

Novel Approaches for Inhibiting the Indoor Allergen Der f 2 Excreted from House Dust Mites by Todomatsu Oil Produced from Woodland Residues.

House dust mite (HDM) is a globally ubiquitous domestic cause of allergic diseases. There is a pressing demand to discover efficient, harmless, and eco-friendly natural extracts to inhibit HDM allergens that are more likely to trigger allergies and challenging to be prevented entirely. This study, therefore, is aimed at assessing the inhibition of the allergenicity of major HDM allergen Der f 2 by todomatsu oil extracted from residues of Abies Sachalinensis. The inhibition was investigated experimentally (using enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)) and in silico using molecular docking. The results showed that todomatsu oil inhibits the allergenicity of Der f 2 by reducing its amount instead of the IgG binding capacity of a single protein. Moreover, the compounds in todomatsu oil bind to Der f 2 via alkyl hydrophobic interactions. Notably, most compounds interact with the hydrophobic amino acids of Der f 2, and seven substances interact with CYS27. Contrarily, the principal compounds fail to attach to the amino acids forming the IgG epitope in Der f 2. Interestingly, chemical components with the lowest relative percentages in todomatsu oil show high-affinity values on Der f 2, especially ß-maaliene (-8.0 kcal/mol). In conclusion, todomatsu oil has been proven in vitro as a potential effective public health strategy to inhibit the allergenicity of Der f 2.

Anti-inflammatory and PTP1B inhibitory sesquiterpenoids from the twigs and leaves of Aglaia lawii.

Twelve sesquiterpenoids with seven different carbon skeletons, including four isodaucanes (1-4), an aromadendrane (5), a guaiane (6), a cadalane (7), two eudesmanes (8 and 9), two bisabolanes (10 and 11), and a megastigmane (12), were isolated from the twigs and leaves of Aglaia lawii (Wight) C. J. Saldanha et Ramamorthy. Of these compounds, amouanglienoids A (1) and B (2) are new isodaucane sesquiterpenoids. This is the first report of isodaucanes from the genus Aglaia, and amouanglienoid A (1) represents the first isodaucane containing a Δ7(8) double bond. Their structures were discerned from extensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison of the experimental and calculated ECD data. In in vitro bioassays, compounds 1, 10, and 11 showed potent inhibitory effects against lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells, while compound 11 exhibited considerable inhibition of PTP1B with an IC50 value of 16.05 ± 1.09 µM.

Stereochemical insights into neuroprotective alkaloids from the aerial parts of Emilia sonchifolia.

A new alkaloid featured with a dibenz[c,e]azepin-5-one scaffold, namely emililactam A (3), together with a known pyrrolidine alkaloid (emilisonchine, 1) and a known flavonoid alkaloid [8-(2″-pyrrolidinone-5″-yl)-quercetin, 2] were isolated from the aerial parts of Emilia sonchifolia. Compounds 1 and 2 were isolated as racemic forms which were further separated, for the first time, to their corresponding enantiomers [(+)-1/(-)-1 and (+)-2/(-)-2], respectively, by using chiral-phase HPLC. The structure of new compound 3 was elucidated by extensive spectroscopic analysis. In addition, the absolute configurations of optically pure (+)-1/(-)-1 and (+)-2/(-)-2 were determined by the time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) calculations. In an in vitro bioassay, compounds (+)-1, (-)-1, (±)-1, and 3 exhibited moderate neuroprotective effects against corticosterone-induced injuries of PC12 cells.

Traditional Chinese medicine promotes bone regeneration in bone tissue engineering.

Bone tissue engineering (BTE) is a promising method for the repair of difficult-to-heal bone tissue damage by providing three-dimensional structures for cell attachment, proliferation, and differentiation. Traditional Chinese medicine (TCM) has been introduced as an effective global medical program by the World Health Organization, comprising intricate components, and promoting bone regeneration by regulating multiple mechanisms and targets. This study outlines the potential therapeutic capabilities of TCM combined with BTE in bone regeneration. The effective active components promoting bone regeneration can be generally divided into flavonoids, alkaloids, glycosides, terpenoids, and polyphenols, among others. The chemical structures of the monomers, their sources, efficacy, and mechanisms are described. We summarize the use of compounds and medicinal parts of TCM to stimulate bone regeneration. Finally, the limitations and prospects of applying TCM in BTE are introduced, providing a direction for further development of novel and potential TCM.