Mulberry branch fiber improved lipid metabolism and egg yolk fatty acid composition of laying hens via the enterohepatic axis.

BACKGROUND: The utilization of mulberry branch fiber (MF), the largest by-product of the sericulture industry, is an important issue. Supplementation with MF as a dietary fiber for poultry may serve as a useful application. However, little is known about the effects of MF on liver lipid metabolism and egg yolk fatty acid composition of laying hens and their underlying mechanisms. In this study, we performed a multi-omics investigation to explore the variations in liver lipid metabolism, egg yolk fatty acid composition, gut microbiota, and the associations among them induced by dietary MF in laying hens. RESULTS: Dietary MF had no harmful effects on the laying performance or egg quality in laying hens. The enzyme activities associated with lipid metabolism in the liver were altered by the addition of 5% MF, resulting in reduced liver fat accumulation. Furthermore, dietary 5% MF induced the variation in the fatty acid profiles of egg yolk, and increased the polyunsaturated fatty acid (PUFA) content. We observed a significant reduction in the diversity of both gut bacteria and changes in their compositions after the addition of MF. Dietary MF significantly increased the abundance of genes involved in fatty acid biodegradation, and short-chain fatty acids biosynthesis in the gut microbiota of laying hens. The significant correlations were observed between the liver lipid metabolism enzyme activities of hepatic lipase, lipoprotein lipase, and total esterase with gut microbiota, including negative correlations with gut microbiota diversity, and multiple correlations with gut bacteria and viruses. Moreover, various correlations between the contents of PUFAs and monounsaturated fatty acids in egg yolk with the gut microbiota were obtained. Based on partial-least-squares path modeling integrated with the multi-omics datasets, we deduced the direct effects of liver enzyme activities and gut bacterial compositions on liver fat content and the roles of liver enzyme activities and gut bacterial diversity on egg yolk fatty acid composition. CONCLUSIONS: The results indicate that dietary MF is beneficial to laying hens as it reduces the liver fat and improves egg yolk fatty acid composition through the enterohepatic axis. Video Abstract.

Do all algae grow faster in environments replenished by reclaimed water? Examples of two effluents produced in Beijing.

Reclaimed water with nitrogen, phosphorus, and other contaminants may trigger algal blooms during its ecological utilization in replenishing rivers or lakes. However, the effect of reclaimed water on algal growth rates is not well understood. In this study, the growth potentials of algae in terms of Cyanophyta, Chlorophyta, and Bacillariophyta, as well as mixed algae in both regular culture medium and reclaimed water produced from treatment plants in Beijing with similar N and P concentrations, were compared to evaluate whether reclaimed water could facilitate algal growth. In addition, reclaimed water was also sterilized to verify the impact of bacteria's presence on algal growth. The results indicated that most algae grew faster in reclaimed water, among which the growth rate of Microcystis aeruginosa even increased by 5.5 fold. The growth of mixed algae in reclaimed water was not enhanced due to the strong adaptive ability of the community structure. Residual bacteria in the reclaimed water were found to be important contributors to algal growth. This work provided theoretical support for the safe and efficient utilization of reclaimed water.

Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial.

Importance: Adjuvant and neoadjuvant immunotherapy have improved clinical outcomes for patients with early-stage non-small cell lung cancer (NSCLC). However, the optimal combination of checkpoint inhibition with chemotherapy remains unknown. Objective: To determine whether toripalimab in combination with platinum-based chemotherapy will improve event-free survival and major pathological response in patients with stage II or III resectable NSCLC compared with chemotherapy alone. Design, Setting, and Participants: This randomized clinical trial enrolled patients with stage II or III resectable NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC) from March 12, 2020, to June 19, 2023, at 50 participating hospitals in China. The data cutoff date for this interim analysis was November 30, 2022. Interventions: Patients were randomized in a 1:1 ratio to receive 240 mg of toripalimab or placebo once every 3 weeks combined with platinum-based chemotherapy for 3 cycles before surgery and 1 cycle after surgery, followed by toripalimab only (240 mg) or placebo once every 3 weeks for up to 13 cycles. Main Outcomes and Measures: The primary outcomes were event-free survival (assessed by the investigators) and the major pathological response rate (assessed by blinded, independent pathological review). The secondary outcomes included the pathological complete response rate (assessed by blinded, independent pathological review) and adverse events. Results: Of the 501 patients randomized, 404 had stage III NSCLC (202 in the toripalimab + chemotherapy group and 202 in the placebo + chemotherapy group) and 97 had stage II NSCLC and were excluded from this interim analysis. The median age was 62 years (IQR, 56-65 years), 92% of patients were male, and the median follow-up was 18.3 months (IQR, 12.7-22.5 months). For the primary outcome of event-free survival, the median length was not estimable (95% CI, 24.4 months-not estimable) in the toripalimab group compared with 15.1 months (95% CI, 10.6-21.9 months) in the placebo group (hazard ratio, 0.40 [95% CI, 0.28-0.57], P < .001). The major pathological response rate (another primary outcome) was 48.5% (95% CI, 41.4%-55.6%) in the toripalimab group compared with 8.4% (95% CI, 5.0%-13.1%) in the placebo group (between-group difference, 40.2% [95% CI, 32.2%-48.1%], P < .001). The pathological complete response rate (secondary outcome) was 24.8% (95% CI, 19.0%-31.3%) in the toripalimab group compared with 1.0% (95% CI, 0.1%-3.5%) in the placebo group (between-group difference, 23.7% [95% CI, 17.6%-29.8%]). The incidence of immune-related adverse events occurred more frequently in the toripalimab group. No unexpected treatment-related toxic effects were identified. The incidence of grade 3 or higher adverse events, fatal adverse events, and adverse events leading to discontinuation of treatment were comparable between the groups. Conclusions and Relevance: The addition of toripalimab to perioperative chemotherapy led to a significant improvement in event-free survival for patients with resectable stage III NSCLC and this treatment strategy had a manageable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT04158440.

Effects of zinc supplementation from organic and inorganic sources on growth, blood biochemical indices, and intestinal microarchitecture in broilers.

In poultry nutrition, zinc supplementation is typically achieved through the addition of zinc oxide or zinc sulfate to the feed. The alternative approach of organic sources utilizes an organic ligand to bind zinc (Zn), resulting in higher bioavailability. Thus, a study was conducted to assess and compare the impact of a methionine-complexed Zn versus an inorganic Zn on growth, blood biochemical profile, gut histomorphology, and fecal excretion of Zn in broilers. The experimental design included two treatments: the addition of a zinc amino acid complex or zinc oxide to the basal diet. The zinc amino acid complex was supplemented at a dose equivalent to the inorganic zinc (Zn-80), while the organic zinc was provided at levels of 20, 40, and 80 mg/kg to a total of 400 broilers. There were five treatments in total, and each treatment was replicated four times. Broilers supplemented with an organic form of Zn at the level of 80 mg/kg had significantly (p < 0.05) higher body weight gain and lower feed conversion ratio (F/G). Significantly (p < 0.05) higher Zn excretion was recorded in broilers supplemented with inorganic Zn supplementation. Significantly (p < 0.05) higher villus length and width, their ratio, and lower (p < 0.05) crypt depth were observed in birds supplemented with 80 mg/kg organic Zn. From the results of the present study, it was concluded that Zn from an organic source at the rate of 80 mg/kg was superior in terms of growth performance, intestinal histomorphology and less excretion of Zn to the environment in broilers.

Extraction of functional natural products employing microwave-assisted aqueous two-phase system: application to anthocyanins extraction from mulberry fruits.

Aqueous two-phase extraction (ATPE) has been extensively utilized for the extraction and separation of tiny-molecule substances as a new system (system with short-chain ethanol and inorganic salts). In this study, an innovative method of extracting anthocyanins from mulberry was developed, employing microwave-assisted extraction with ethanol/ammonium sulfate as a biphasic extractant. Response surface methodology (RSM) was utilized to optimize anthocyanin extraction conditions: 39% ethanol (w/w), 13% ammonium sulfate (w/w), and liquid-to-solid ratio of 45:1, microwave duration 3 min, microwave temperature 32 °C, and microwave power 480 Watt (W). High-performance liquid chromatography (HPLC) analysis demonstrated no significant differences in the structure of mulberry anthocyanins before and after MAATPE treatment, furthermore. The extraction behavior of MAATPE was due to hydrogen bonding, according to Fourier transform infrared spectroscopy (FT-IR). Scanning electron microscopy analysis found that MAATPE damaged the cell structure via a microwave enhancement effect, which was more favorable to anthocyanin dissolution than standard extraction methods. The DPPH free radical scavenging rate of mulberry extracts at 0.5 mg/mL was higher than that of vitamin C (96.4 ± 0.76%), and the ABTS free radical scavenging rate (82.52 ± 2.13%) was close to that of vitamin C, indicating that MAATPE-derived mulberry extracts have good antioxidant activity.

Nitrogen and phosphorus removal performance of sequential batch operation for algal cultivation through suspended-solid phase photobioreactor.

Nitrogen (N) and phosphorus (P) absorbed by algae in the suspended-solid phase photobioreactor (ssPBR) have emerged as an efficient pathway to purify the effluent of wastewater treatment plants (WWTPs). However, the key operational parameters of the ssPBR need to be optimized. In this study, the stability of the system after sequential batch operations and the efficiency under various influent P concentrations were evaluated. The results demonstrated that the ssPBR maintained a high N/P removal efficiency of 96 % and 98 %, respectively, after 5 cycles. When N was kept at 15 mg/L and P ranged from 1.5 to 3.0 mg/L, the system yielded plenty of algae products and guaranteed the effluent quality that met the discharge standards. Notably, the carriers were a key contributor to the high metabolism of algae and high performance. This work provided theoretical ideas and technical guidance for effluent quality improvement in WWTPs.

Chemical profiling and mechanistic studies of Zhi-Shang-Feng granules against influenza virus by high-performance liquid chromatography coupled with Q exactive focus hybrid quadrupole orbitrap high-resolution mass spectrometry in combination with network pharmacology analysis.

Zhi-Shang-Feng Granules are used in the clinical treatment of influenza to relieve headaches, chills and fever, bronchitis, nasal congestion, neuralgia and other symptoms. To decipher the components responsible for therapeutic effects of Zhi-Shang-Feng g ranules against influenza virus, an analytical method based on high-performance liquid chromatography coupled with Q exactive focus hybrid quadrupole orbitrap high resolution mass spectrometry was developed and the chemical profile of Zhi-Shang-Feng granules was characterized. Then, the identified components were used to conduct network pharmacological analysis and determine the potential mechanism of Zhi-Shang-Feng Granules. As a result, 177 compounds were putatively identified through comprehensive analysis by liquid chromatography coupled with high-resolution mass spectrometry, of which 23 compounds were unambiguously confirmed with reference standards. Components in Zhi-Shang-Feng Granules were found to specifically act on different enzymes, G-protein-coupled receptors, ion channels and transporters in the immune, endocrine, nervous, and circulatory systems. The potential mechanism was related to several biological processes, including cell growth and death, pattern recognition receptor signalling, signalling by interleukins, and lipid metabolism. The combination of chemical profile characterization and network construction provided useful insight into the overall chemical composition of Zhi-Shang-Feng granules and revealed their potential anti-infection, anti-inflammatory and immunoregulatory mechanisms against influenza virus infected disease.

Biphasic Dose-Response of Mn-Induced Mitochondrial Damage, PINK1/Parkin Expression, and Mitophagy in SK-N-SH Cells.

Excessive manganese (Mn) exposure produces neurotoxicity with mitochondrial damage. Mitophagy is a protective mechanism to eliminate damaged mitochondria to protect cells. The aim of this study was to determine the dose-response of Mn-induced mitochondria damage, the expression of mitophagy-mediated protein PINK1/Parkin and mitophagy in dopamine-producing SK-N-SH cells. Cells were exposed to 0, 300, 900, and 1500 µM Mn2+ for 24 h, and ROS production, mitochondrial damage and mitophagy were examined. The levels of dopamine were detected by ELISA and neurotoxicity and mitophagy-related proteins (α-synuclein, PINK1, Parkin, Optineurin, and LC3II/I) were detected by western blot. Mn increased intracellular ROS and apoptosis and decreased mitochondrial membrane potential in a concentration-dependent manner. However, at the low dose of 300 µM Mn, autophagosome was increased 11-fold, but at the high dose of 1500 µM, autophagosome was attenuated to 4-fold, together with decreased mitophagy-mediated protein PINK1/Parkin and LC3II/I ratio and increased Optineurin expression, resulting in increased α-synuclein accumulation and decreased dopamine production. Thus, Mn-induced mitophagy exhibited a novel biphasic regulation: at the low dose, mitophagy is activated to eliminate damaged mitochondria, however, at the high dose, cells gradually loss the adaptive machinery, the PINK1/Parkin-mediated mitophagy weakened, resulting in neurotoxicity.

Secoiridoids from the traditional Chinese medicine Swertia pseudochinensis.

Detailed phytochemical investigation on the traditional Chinese medicine Swertia pseudochinensis Hara led to the isolation of ten undescribed secoiridoids and fifteen known analogs. Their structures were elucidated by extensive spectroscopic analysis (including 1D and 2D NMR, and HRESIMS). Selected isolates were assayed for their anti-inflammatory and antibacterial activities, and moderate anti-inflammatory activity via inhibiting the secretion of cytokines IL-6 and TNF-α in macrophages RAW264.7 induced by LPS were observed. Antibacterial activity against Staphylococcus aureus was not found at 100 µM.

Yi-Shen-Hua-Shi granule ameliorates diabetic kidney disease by the "gut-kidney axis".

ETHNOPHARMACOLOGICAL RELEVANCE: Yi-Shen-Hua-Shi (YSHS) granule is an effective prescription widely used in traditional Chinese medicine to treat diabetic kidney disease (DKD), its exact efficacy in treating DKD has been confirmed but the underlying regulatory mechanism has not been fully elucidated. AIM OF THE STUDY: To explore the mechanism by which YSHS granule regulates intestinal flora and serum metabolites and then regulates renal mRNA expression through the "gut-kidney axis", so as to improve DKD. MATERIALS AND METHODS: 40 rats were divided into five groups: Normal group (N) (normal saline), model group (M) (STZ + normal saline), YSHS granule low-dose group (YL) (STZ + 2.27 g kg-1 d-1), YSHS granule high-dose group (YH) (STZ + 5.54g kg-1 d-1) and valsartan group (V) (STZ + 7.38mg kg-1 d-1). After 6 weeks, changes in blood glucose, blood lipids, and renal function related indexes were observed, as well as pathological changes in the kidney and colon. Intestinal microbiota was sequenced by 16S rDNA, serum differential metabolites were identified by LC-MS/MS, and renal differences in mRNA expression were observed by RNA-seq. Further, through the association analysis of intestinal differential microbiota, serum differential metabolites and kidney differential mRNAs, the target flora, target metabolites and target genes of YSHS granule were screened and verified, and the "gut-metabolism-transcription" co-expression network was constructed. RESULTS: In group M, blood glucose, blood lipid and proteinuria were increased, inflammation, oxidative stress and renal function were aggravated, with the proliferation of mesangial matrix, vacuolar degeneration of renal tubules, accumulation of collagen and lipid, and increased intestinal permeability, and YSHS granule and valsartan improved these disorders to varying degrees. High dose of YSHS granule improved the diversity and abundance of flora, decreased the F/B value, greatly increased the abundance of Lactobacillus and Lactobacillus_murinus, and decreased the abundance of Prevoella UCG_001. 14 target metabolites of YSHS granule were identified, which were mainly enriched in 20 KEGG pathways, such as Glycerophospholipid metabolism, Sphingolipid metabolism and Phenylalanine, tyrosine and tryptophan biosynthesis. 96 target mRNAs of YSHS granule were also identified. The enriched top 20 pathways were closely related to glucose and lipid metabolism, of which a total of 21 differential mRNAs were expressed. Further correlation analysis revealed that Lactobacillus, Lactobacillus_murinus and Prevotella UCG_001 were highly correlated with Glycerophospholipid metabolism, Sphingolipid metabolism and Phenylalanine, tyrosine and tryptophan biosynthesis pathways. At the same time, 6 pathways including Glycerophospholipid metabolism, Arachidonic acid metabolism, Purine metabolism, Primary bile acid biosynthesis, Ascorbate and aldarate metabolism and Galactose metabolism were co-enriched by the target metabolites and the target mRNAs of YSHS granule, including 7 differential metabolites such as phosphatidylethanolamine and 7 differential genes such as Adcy3. The 7 differential metabolites had high predictive value of AUC, and the validation of 7 differential genes were highly consistent with the sequencing results. CONCLUSION: YSHS granule could improve DKD through the "gut-kidney axis". Lactobacillus and Lactobacillus_murinus were the main driving forces. 6 pathways related to glucose and lipid metabolism, especially Glycerophospholipid metabolism, may be an important follow-up response and regulatory mechanism.

Investigating continuation of folic acid supplementation during peri-conceptional period: a community-based cross-sectional study.

BACKGROUND: Maternal folate may not reach an optimal level to prevent neural tube defects if supplementation commenced post-conception or took place pre-conception only. Our study aimed to investigate the continuation of folic acid (FA) supplementation from pre-conception to post-conception during peri-conceptional period and to examine its differences in FA supplementation between the subgroups taking the initiation timing into consideration. METHODS: This study was conducted in two community health service centers in Jing-an District of Shanghai. Women accompanying their children to pediatric health clinics of the centers were recruited and asked to recall information concerning their socioeconomic and previous obstetric characteristics, utilization of healthcare and FA supplementation before and/or during pregnancy. The continuation of FA supplementation during peri-conceptional period were categorized into three subgroups: Supplementing with FA pre- and post-conception; supplementing with FA preconception only or post-conception only; no FA supplements pre-conception and post-conception. The relationship between FA continuation and couples' characteristics were examined as setting the first subgroup as the base reference. RESULTS: Three hundred and ninety-six women were recruited. Over 40% of the women started FA supplementation after conception and 30.3% of them supplemented with FA from pre-conception to the first trimester of their pregnancy. Compared to this one-third of participants, women who didn't supplemented with any FA during peri-conceptional period were more likely to have no utilization of pre-conception healthcare ([Formula: see text]= 2.47, 95% [Formula: see text]: 1.33-4.61) or antenatal care ([Formula: see text]= 4.05, 95% [Formula: see text]: 1.76-9.34), or who had a lower family socioeconomic status ([Formula: see text]= 4.36, 95% [Formula: see text]: 1.79-10.64). Women who supplemented with FA pre-conception only or post-conception only were more likely to have no utilization of pre-conception healthcare ([Formula: see text]= 2.94, 95% [Formula: see text]: 1.79-4.82), or to have no previous pregnancy complication ([Formula: see text]=1.80, 95% [Formula: see text]: 0.99-3.28). CONCLUSION: Over two-fifth of the women started FA supplementation and only one-third of them had an optimal supplementation from pre-conception to the first trimester. Maternal utilization of healthcare before or during pregnancy together with maternal and paternal socioeconomic status may play a role in the continuation to FA supplementation pre- and post-conception.

Secondary metabolites from the Mongolian medicine Lomatogonium carinthiacum.

Systematic phytochemical investigation on the Mongolian medicinal herb Lomatogonium carinthiacum led to the isolation of 12 monoterpenoids including three new secoiridoids (1, 2 and 4) and one new iridoid glycoside (13), one new monoterpenoid alkaloid (3), and three new sesquiterpenoids (14-16). Comprehensive spectroscopic analysis (including 1D and 2D NMR, and HRESIMS) and quantum chemistry computations (including ECD and NMR calculations) were applied to elucidate their structures. Weak immunosuppressive activities were observed for the new isolates via inhibiting T cell proliferation and cytokine IFN-γ secretion in vitro.

Transcatheter Arterial Embolization Combined with Anti-vascular Agent Combretastatin A4 Phosphate Inhibits Growth and Vascularization of Liver Tumor in an Animal Model.

OBJECTIVE: This study aimed to investigate the effect of combretastatin A4 phosphate (CA4P) on proliferation, migration, and capillary tube formation of human umbilical vein endothelial cells (HUVECs) and the efficacy of transcatheter arterial embolization combined with CA4P in the treatment of rabbit VX2 liver tumor. METHODS: The effects of different concentrations of CA4P on proliferation, migration and capillary tube formation of HUVECs were investigated by cell proliferation assay, wound healing assay and capillary tube formation assay, respectively. Thirty-two rabbits implanted with liver VX2 tumors were randomly divided into 4 groups. After catheterization of the left hepatic artery, the infusion was performed using normal saline (group A), CA4P aqueous solution (group B), lipiodol and polyvinyl alcohol particles (group C), and CA4P lipiodol emulsion and polyvinyl alcohol particles (group D), respectively. Half of the animals in each group were euthanized for immunohistochemical analysis to evaluate microvessel density (MVD) at 3 days post-treatment. The other half were examined by MRI and histology to evaluate tumor growth and necrosis at 7 days post-treatment. RESULTS: CA4P could inhibit the proliferation, migration, and tube formation of HUVECs in cell experiments. After interventional treatment, the level of MVD in group D was lower than that in group C (P<0.01). The tumor volume in group C or D was lower than that in group A or B (P<0.01). The tumor necrosis rate was higher in group D than in the other groups. CONCLUSION: The study suggests that CA4P could inhibit the proliferation, migration, and capillary tube formation of HUVECs, and transcatheter arterial embolization combined with CA4P could inhibit the growth of VX2 tumor and obviously induce tumor necrosis.

Effect of Dietary Fructus mume and Scutellaria baicalensis Georgi on the Fecal Microbiota and Its Correlation with Apparent Nutrient Digestibility in Weaned Piglets.

Traditional Chinese medicine (TCM) has long been demonstrated to exert a therapeutic effect on various diseases and has been used as a substitute for antibiotics in pig production. However, few studies have investigated the relationship between the intestinal microbiota and apparent nutrient digestibility when weaned piglet diets are supplemented with TCM. One hundred and sixty-two 25-day-old weaning piglets were housed in an environmentally controlled nursery facility and fed a basal diet (control group, n = 54) or a TCM complex (Fructus mume 1%, Scutellaria baicalensis Georgi 3%) (TCM group, n = 54), or a fermented diet with a complex of these two TCMs (F-TCM group, n = 54). Compared with the control group, in the TCM and F-TCM groups, the average daily gain (ADG) increased (p < 0.05), the F:G ratio and diarrhea rate decreased (p < 0.05), and the apparent digestibility of dry matter (DM) and ether extract (EE) of weaned piglets increased (p < 0.05). Bacteroidetes and Firmicutes were the predominant phyla, representing approximately 95% of all sequences. The abundance of four genera and 10 OTUs (belonging to Ruminococcaceae_UCG-014, Lachnoclostridium, Prevotellaceae_NK3B31 group, Prevotella_1) were negatively correlated with apparent EE digestibility (p < 0.05). The results suggest that weaned piglets fed with antibiotic-free diets supplemented with Fructus mume and Scutellaria baicalensis Georgi gained more weight and were healthier. When added to the diet, the complex of these two TCMs may have a direct impact on apparent EE digestibility by modifying the gut microbial composition, which favors the health of weaned piglets.

The Impact of Zinc Supplementation on Critically Ill Patients With Acute Kidney Injury: A Propensity Score Matching Analysis.

Background: Zinc is an essential trace element involved in multiple metabolic processes. Acute kidney injury (AKI) is associated with low plasma zinc, but outcomes with zinc supplementation in critically ill patients with AKI remain unknown. Our objective was to investigate the effectiveness of zinc supplementation in this patient population. Methods: Critically ill patients with AKI were identified from the Medical Informative Mart for Intensive Care IV database. Prosperity score matching (PSM) was applied to match patients receiving zinc treatment to those without zinc treatment. The association between zinc sulfate use and in-hospital mortality and 30-day mortality, need for renal replacement therapy (RRT), and length of stay was determined by logistic regression and Cox proportional hazards modeling. Results: A total of 9,811 AKI patients were included in the study. PSM yielded 222 pairs of patients who received zinc treatment and those who did not. Zinc supplementation was associated with reduced in-hospital mortality (HR = 0.48 (95% CI: 0.28, 0.83) P = 0.009) and 30-day mortality (HR = 0.51 (95% CI, 0.30, 0.86) P = 0.012). In the subgroup analysis, zinc use was associated with reduced in-hospital mortality in patients with stage 1 AKI and those with sepsis. Conclusions: Zinc supplementation was associated with improved survival in critically ill patients with AKI. The supplementation was especially effective in those with stage 1 AKI and sepsis. These results need to be verified in randomized controlled trials.

(±)-Walskiiglucinol A, a pair of rearranged acylphloroglucinol derivative enantiomers from Hypericum przewalskii.

(±)-Walskiiglucinol A (1a/1b), a pair of rearranged acylphloroglucinol derivatives with a new carbon skeleton, was obtained from Hypericum przewalskii. Compounds 1a/1b were the first examples of naturally occurring acylphloroglucinol derivatives possessing a unique 1-oxaspiro[4.4]nonane core bearing a new 5/5 ring system. Their planar and relative structures were identified by extensive spectroscopic analysis and NMR chemical shift calculations with DP4+ probability analysis, and their absolute configurations were determined by electronic circular dichroism (ECD) calculations. A plausible biogenetic pathway of 1a/1b was proposed in which the breakage of the C-2/C-3 linkage via a retro-Claisen reaction and the cyclization between C-3 and C-1 were proposed as key steps. The isolates were evaluated for cytotoxic activities against a panel of cancer cell lines and anti-inflammatory activities against lipopolysaccharide (LPS)-induced NO production, and compounds 1a/1b showed moderate cytotoxic activities with IC50 values ranging from 9.72 to 36.75 µM.

Norprzewalsone A, a Rearranged Polycyclic Polyprenylated Acylphloroglucinol with a Spiro[cyclopentane-1,3'-tricyclo[7.4.0.01,6]tridecane] Core from Hypericum przewalskii.

Norprzewalsone A (1), a rearranged polyprenylated polycyclic acylphloroglucinol (PPAP) with a new carbon skeleton, along with a new congener, norprzewalsone B (2), were isolated from Hypericum przewalskii. Compound 1 possessed a new 5/6/5/6/6 pentacyclic ring system based on a spiro[cyclopentane-1,3'-tricyclo[7.4.0.01,6]tridecane] core, which might be derived from the common [3.3.1]-type bicyclic polyprenylated acylphloroglucinol (BPAP) via the key retro-Claisen, intramolecular cyclization, and Diels-Alder cyclization reactions. Their structures and absolute configurations were confirmed by spectroscopic data, calculated 1D NMR data with DP4+ probability analyses, and electronic circular dichroism calculations and comparison. More significantly, compound 1 exhibited a moderate inhibitory effect on NO production in lipopolysaccharide-stimulated RAW264.7 cells.

Kiiacylphnols A-H, eight undescribed polycyclic polyprenylated acylphloroglucinols with anticancer activities from Hypericum przewalskii Maxim.

Kiiacylphnols A-H, eight previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs), along with two known congeners (hyperforcinol F and oxepahyperforin), were obtained from Hypericum przewalskii Maxim. The structures of these metabolites were confirmed by spectroscopic analyses, quantum-chemical 1H and 13C NMR calculations with DP4+ analyses, electronic circular dichroism (ECD) comparisons and calculations. Kiiacylphnols A and B were the first [3.3.1]-type PPAPs with an unusual octahydrooxireno[2,3-i]chromene scaffold bearing a rare 6/6/6/3 ring system. More significantly, kiiacylphnol A and oxepahyperforin displayed cytotoxicity against acute myeloid leukemia and diffuse large B-cell lymphoma cell lines by inducing cell apoptosis.

Discovery of Undescribed Monoterpenoid Polyprenylated Acylphloroglucinols with Immunosuppressive Activities from Hypericum longistylum.

Acylphlorostylums A-G (1-7), seven undescribed monoterpenoid polyprenylated acylphloroglucinols, were isolated and identified from Hypericum longistylum. Significantly, acylphlorostylums A and B were the first monoterpenoid polyprenylated acylphloroglucinols possessing a dodecahydro-1H-benzo [b]cyclopenta [e]oxepine moiety bearing a 6/7/5 fused tricyclic ring system that assembled by the attack from 4-OH to C-13. In addition, acylphlorostylums A-G exhibited moderate in vitro immunosuppressive activity in anti-CD3/anti-CD28 monoclonal antibodies, lipopolysaccharide and concanavalin A-induced murine splenocyte proliferation, with IC50 values ranging from 1.51 ± 0.12 to 18.49 ± 1.67 µM, underscoring those isolates as novel chemical templates in the development of novel immunosuppressors.

Discovery of immunosuppressive Lupane-type Triterpenoids from Hypericum longistylum.

The phytochemistry study of Hypericum longistylum afforded one new degraded lupane-type triterpenoid, triterhyper A (1), and seven known congeners (2-8). The structures of those natural products were identified by extensive spectroscopic techniques and single crystal diffraction tests. Notably, triterhyper A (1) possessing an unusual 28-nor-lupane skeleton. More significantly, compounds 1-3 exhibited potential inhibitory effects on murine splenocytes proliferation stimulated by anti-CD3/anti-CD28 monoclonal antibodies (mAbs) and lipopolysaccharide (LPS), with IC50 values ranging from (4.56 ± 0.45) µM to (18.34 ± 2.34) µM, highlighting that those isolates as potential lead compounds in the development of immunosuppressive drugs for autoimmune disease treatment.