The complete chloroplast genome and phylogenetic analysis of Elaeagnus oldhamii (Elaeagnaceae) from Fujian, southeastern China.

Elaeagnus oldhamii Maximowicz 1870 is an important medicinal plant mainly distributing in the southeastern coastal region of China. However, the complete chloroplast genome of E. oldhamii has never been studied at present. We obtained the complete chloroplast genome of E. oldhamii, which was 152,283 bp in length, with a typical quadripartite structure that includes a large single-copy region of 82,229 bp, a small single-copy region of 18,256 bp, and 2 inverted repeat (IR) regions of 25,899 bp. The genome contained 128 unique genes with a GC content of 37%, including 83 protein-coding genes, 37 tRNAs, and 8 rRNAs. Phylogenetic analysis suggested that E. oldhamii was closely related to E. glabra and E. macrophylla.

Identification of Bulbocodin D and C as novel STAT3 inhibitors and their anticancer activities in lung cancer cells.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC50s for BD and BC were 11.63 and 11.71 µmol·L-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.

Baicalin attenuated metabolic dysfunction-associated fatty liver disease by suppressing oxidative stress and inflammation via the p62-Keap1-Nrf2 signalling pathway in db/db mice.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the main cause of chronic liver disease. Baicalin (Bai), a bioactive molecule found in Scutellaria baicalensis Georgi, possesses antioxidant and antiinflammatory properties. These activities suggest Bai could be a promising therapeutic agent against NAFLD; however, its specific effects and underlying mechanism are still not clear. This study aims to explore the effect of Bai to attenuate MAFLD and associated molecular mechanisms. Bai (50, 100 or 200 mg/kg) was orally administered to db/db mice with MAFLD for 4 weeks or db/m mice as the normal control. Bai markedly attenuated lipid accumulation, cirrhosis and hepatocytes apoptosis in the liver tissues of MAFLD mice, suggesting strong ability to attenuate MAFLD. Bai significantly reduced proinflammatory biomarkers and enhanced antioxidant enzymes, which appeared to be modulated by the upregulated p62-Keap1-Nrf2 signalling cascade; furthermore, cotreatment of Bai and all-trans-retinoic acid (Nrf2 inhibitor) demonstrated markedly weakened liver protective effects by Bai and its induced antioxidant and antiinflammatory responses. The present study supported the use of Bai in attenuating MAFLD as a promising therapeutic agent, and its strong mechanism of action in association with the upregulating the p62-keap1-Nrf2 pathway.

Magnolol as STAT3 inhibitor for treating multiple sclerosis by restricting Th17 cells.

OBJECTIVE: Multiple sclerosis (MS) is an immune disease in the central nervous system (CNS) associated with Th17 cells. Moreover, STAT3 initiates Th17 cell differentiation and IL-17A expression through facilitating RORγt in MS. Here, we reported that magnolol, isolated from Magnolia officinalis Rehd. Et Wils, was regarded as a candidate for MS treatment verified by both in vitro and in vivo studies. METHODS: In vivo, experimental autoimmune encephalomyelitis (EAE) model in mice was employed to evaluate the alleviation of magnolol on myeloencephalitis. In vitro, FACS assay was employed to evaluate the effect of magnolol on Th17 and Treg cell differentiation and IL-17A expression; network pharmacology-based study was applied to probe the involved mechanisms; western blotting, immunocytochemistry, and luciferase reporter assay was used to further confirm the regulation of magnolol on JAK/STATs signaling pathway; surface plasmon resonance (SPR) assay and molecular docking were applied to manifest affinity with STAT3 and binding sites; overexpression of STAT3 was employed to verify whether magnolol attenuates IL-17A through STAT3 signaling pathway. RESULTS: In vivo, magnolol alleviated loss of body weight and severity of EAE mice; magnolol improved lesions in spinal cords and attenuated CD45 infiltration, and serum cytokines levels; correspondingly, magnolol focused on inhibiting Th17 differentiation and IL-17A expression in splenocyte of EAE mice; moreover, magnolol selectively inhibited p-STAT3(Y705) and p-STAT4(Y693) of both CD4+ and CD8+ T cells in splenocyte of EAE mice. In vitro, magnolol selectively inhibited Th17 differentiation and IL-17A expression without impact on Treg cells; network pharmacology-based study revealed that magnolol perhaps diminished Th17 cell differentiation through regulating STAT family members; western blotting further confirmed that magnolol inhibited p-JAK2(Y1007) and selectively antagonized p-STAT3(Y705) and slightly decreased p-STAT4(Y693); magnolol antagonized both STAT3 nucleus location and transcription activity; magnolol had a high affinity with STAT3 and the specific binding site perhaps to be at SH2 domain; overexpression of STAT3 resulted in failed inhibition of magnolol on IL-17A. CONCLUSION: Magnolol selectively inhibited Th17 differentiation and cytokine expression through selectively blocking of STAT3 resulting in decreased the ratio of Th17/Treg cells for treating MS, suggesting that the potential of magnolol for treating MS as novel STAT3 inhibitor.

Pien Tze Huang attenuated acetaminophen-induced liver injury by autophagy mediated-NLRP3 inflammasome inhibition.

ETHNOPHARMACOLOGICAL RELEVANCE: Pien Tze Huang is a classic traditional Chinese medicinal product, used for inflammatory diseases as stated in Chinese Pharmacopoeia. In particular, it is effective in treating liver diseases and pro-inflammatory conditions. Acetaminophen (APAP) is a widely used analgesic drug, but its over-dose is associated with acute liver failure where the clinical approved antidote treatment is limited. Inflammation has been considered as one of the therapeutic targets against APAP-induced liver injury. AIM OF THE STUDY: We aimed to explore the therapeutic potential of Pien Tze Huang tablet (PTH) on protecting liver against APAP-induced liver injury through its strong anti-inflammatory pharmacological action. MATERIALS AND METHODS: Wild-type C57BL/6 mice were given PTH (75, 150 and 300 mg/kg) by oral gavage 3 days before the APAP injection (400 mg/kg). The protective effect of PTH was assessed by aspartate aminotransferase (AST) and alanine transaminase (ALT) levels and pathological staining. The mechanisms underlying PTH's hepatoprotective effects were investigated in nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) knock-out (NLRP3-/-), over expression NLRP3 (oe-NLRP3) mice, and wild-type mice with the injection of autophagy inhibitor (3-methyladenine, 3-MA). RESULTS: APAP-exposed mice resulted in evident liver injury which was evidenced by hepatic necrosis and elevated levels of AST and ALT in the wild-type C57BL/6 mice. PTH dose-dependently reduced ALT, AST and upregulated autophagy activity. In addition, PTH significantly reduced elevated levels of proinflammatory cytokines and NLRP3 inflammasome. The liver protective effect of PTH (300 mg/kg) was still obvious in the oe-NLRP3 mice, however, it became insignificant in the NLRP3-/- mice. When PTH (300 mg/kg) was co-treated with 3-MA to the wild-type C57BL/6 mice, the NLRP3 inhibition were reversed when autophagy was blocked. CONCLUSION: PTH exerted a beneficial effect in protecting liver against APAP-induced liver injury. The underlying molecular mechanism was associated with the NLRP3 inflammasome inhibition which was likely driven by the upregulated autophagy activity. Our study underpins the traditional use of PTH in protecting liver through its anti-inflammatory action.

Phytochemical compositions and biological activities of the branches and leaves of Ormosia hosiei Hemsl. et Wils.

Ormosia hosiei Hemsl. et Wils. is an economical and medicinal plant, increasingly cultivated in China; however, its branches and leaves are often pruned as waste. This is the first study focused on the phytochemical profiles and antioxidant, anti-α-glucosidase, anti-tyrosinase, and anti-neuroinflammatory activities of the branches and leaves of O. hosiei. Herein, thirty-seven characteristic compounds were identified by UPLC-MS/MS and twelve were detected for the first time in O. hosiei. Twenty-seven phenolics were further quantified and significant differences in phenolic compositions between the branches and leaves of O. hosiei were observed. The ethanol extracts exhibited promising antioxidant, anti-α-glucosidase, anti-tyrosinase, and anti-neuroinflammatory effects, and the bioactivities significantly correlated with total phenolic content and twelve individual phenolics. Naringin, genistein, vitexin, vitexin-2-O-rhamnoside, syringaresinol and syringaresinol-4-O-ß-D-glucopyranoside can be considered potential quality markers of O. hosiei. Our results provided solid evidence that the branches and leaves of O. hosiei deserve more attention and exploitation, considering the potential to be developed as functional foods or herbal medicines.

Effect of dendrobium mixture in alleviating diabetic cognitive impairment associated with regulating gut microbiota.

Dendrobium mixture (DM) is a patent Chinese herbal formulation consisting of Dendrobii Caulis, Astragali Radix, Rehmanniae Radix as the main ingredients. DM has been shown to alleviate diabetic related symptoms attributed to its anti-hyperglycaemic and anti-inflammatory activities. However, the effect on diabetic induced cognitive dysfunction has not been investigated. This study aims to investigate the effect of DM in improving diabetic cognitive impairment and associated mechanisms. Our study confirmed the anti-hyperglycaemic effect of DM and showed its capacity to restore the cognitive and memory function in high fat/high glucose and streptozotocin-induced diabetic rats. The neuroprotective effect was manifested as improved learning and memory behaviours, restored blood-brain barrier tight junction, and enhanced expressions of neuronal survival related biomarkers. DM protected the colon tight junction, and effectively lowered the circulated proinflammatory mediators including tumour necrosis factor-α, interleukin-6 and lipopolysaccharides. In the gut microbiota, DM corrected the increase in the abundance of Firmicutes, the increase in the ratio of Firmicutes/Bacteroidetes, and the decrease in the abundance of Bacteroidetes in diabetic rats. It also reversed the abundance of Lactobacillus, Ruminococcus and Allobaculum genera. Short chain fatty acids, isobutyric acid and ethylmethylacetic acid, were negatively and significantly correlated to Ruminococcus and Allobaculum. Isovaleric acid was positively and significantly correlated with Lactobacillus, which all contributing to the improvement in glucose level, systemic inflammation and cognitive function in diabetic rats. Our results demonstrated the potential of DM as a promising therapeutic agent in treating diabetic cognitive impairment and the underlying mechanism may be associated with regulating gut microbiota.

Unprecedented organelle genomic variations in morning glories reveal independent evolutionary scenarios of parasitic plants and the diversification of plant mitochondrial complexes.

BACKGROUND: The morning glories (Convolvulaceae) are distributed worldwide and produce economically important crops, medicinal herbs, and ornamentals. Members of this family are diverse in morphological characteristics and trophic modes, including the leafless parasitic Cuscuta (dodders). Organelle genomes were generally used for studying plant phylogeny and genomic variations. Notably, plastomes in parasitic plants always show non-canonical features, such as reduced size and accelerated rates. However, few organelle genomes of this group have been sequenced, hindering our understanding of their evolution, and dodder mitogenome in particular. RESULTS: We assembled 22 new mitogenomes and 12 new plastomes in Convolvulaceae. Alongside previously known ones, we totally analyzed organelle genomes of 23 species in the family. Our sampling includes 16 leafy autotrophic species and 7 leafless parasitic dodders, covering 8 of the 12 tribes. Both the plastid and mitochondrial genomes of these plants have encountered variations that were rarely observed in other angiosperms. All of the plastomes possessed atypical IR boundaries. Besides the gene and IR losses in dodders, some leafy species also showed gene and intron losses, duplications, structural variations, and insertions of foreign DNAs. The phylogeny reconstructed by plastid protein coding sequences confirmed the previous relationship of the tribes. However, the monophyly of 'Merremieae' and the sister group of Cuscuta remained uncertain. The mitogenome was significantly inflated in Cuscuta japonica, which has exceeded over 800 kb and integrated massive DNAs from other species. In other dodders, mitogenomes were maintained in small size, revealing divergent evolutionary strategies. Mutations unique to plants were detected in the mitochondrial gene ccmFc, which has broken into three fragments through gene fission and splicing shift. The unusual changes likely initially happened to the common ancestor of the family and were caused by a foreign insertion from rosids followed by double-strand breaks and imprecise DNA repairs. The coding regions of ccmFc expanded at both sides after the fission, which may have altered the protein structure. CONCLUSIONS: Our family-scale analyses uncovered unusual scenarios for both organelle genomes in Convolvulaceae, especially in parasitic plants. The data provided valuable genetic resources for studying the evolution of Convolvulaceae and plant parasitism.

Anticancer Effects of Ginsenoside Rh2: A Systematic Review.

BACKGROUND: As one of the effective pharmacological constituents of Ginseng Radix et Rhizoma, ginsenoside Rh2 (Rh2) exerts a remarkable anticancer effect on various cancer cell lines in vitro and strongly inhibits tumor growth in vivo without severe toxicity. OBJECTIVE: This article reviewed existing evidence supporting the anticancer effects of Rh2 to classify and conclude previous and current knowledge on the mechanisms and therapeutic effects of Rh2, as well as to promote the clinical application of this natural product. CONCLUSION: This article reviewed the anticancer efficacies and mechanisms of Rh2, including the induction of cell cycle arrest and programmed cell death, repression of metastasis, alleviation of drug resistance, and regulation of the immune system. Finally, this paper discussed the research and application prospects of Rh2.

Neobaicalein Inhibits Th17 Cell Differentiation Resulting in Recovery of Th17/Treg Ratio through Blocking STAT3 Signaling Activation.

Huangqin is the dried root of Scutellaria baicalensis Georgi, which has been widely utilized for heat-clearing (Qingre) and dewetting (Zaoshi), heat-killed (Xiehuo) and detoxifying (Jiedu) in the concept of Traditional Chinese Medicine and is used for treating inflammation and cancer in clinical formulas. Neobaicalein (NEO) is of flavonoid isolated from Huangqin and has been reported to possess prominent anti-inflammatory effects in published work. Th17/Treg balance shift to Th17 cells is an essential reason for autoimmune inflammatory diseases. However, the role NEO plays in Th17 and Treg and the underlying mechanism has not been elucidated yet. Network pharmacology-based study revealed that NEO predominantly regulated IL-17 signaling pathway. Moreover, our result shown that NEO (3-30 µmol/L) down-regulated Th17 differentiation and cellular supernatant and intracellular IL-17A level and tumor necrosis factor α production in a concentration-dependent manner. The further mechanism research revealed that NEO also specifically inhibited phosphorylation of STAT3(Tyr725) and STAT4 (Y693) without influence on activation of STAT5 and STAT6 in splenocytes. Immunofluorescence results illuminated that NEO effectively blocked STAT3 translocated into nucleus. Interestingly, NEO at appreciated dose could only inhibit Th17 cell differentiation and have no effect on Treg differentiation. The present study revealed that NEO effectively inhibited Th17 cell differentiation through specifically blocking the activation of STAT3 signaling without inactivation of STAT5 and STAT6. Additional inhibitory effect on activation of STAT4 by NEO also suggested the potential for antagonism against Th1 differentiation. All work suggested that NEO may be a potential candidate for immunoregulation and treating autoimmune inflammatory diseases through inhibiting immune cell viability and T cell differentiation.

Pien-Tze-Huang attenuates neuroinflammation in cerebral ischaemia-reperfusion injury in rats through the TLR4/NF-κB/MAPK pathway.

CONTEXT: Pien-Tze-Huang (PTH) is traditionally applied to treat various inflammation-related diseases including stroke. However, literature regarding the anti-inflammatory effects and possible mechanisms of PTH in ischaemic stroke is unavailable. OBJECTIVE: This study investigates the anti-inflammatory effects and its underlying mechanism of PTH on ischaemic stroke. MATERIALS AND METHODS: Cerebral ischaemia-reperfusion injury was induced through 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion in male Sprague-Dawley (SD) rats receiving oral pre-treatment with PTH (180 mg/kg) for 4 days. TLR4 antagonist TAK-242 (3 mg/kg) was injected intraperitoneally at 1.5 h after MCAO. MRI, HE staining, qRT-PCR, western blot, and immunofluorescence methods were employed. RESULTS: PTH treatment markedly reduced cerebral infarct volume (by 51%), improved neurological function (by 33%), and ameliorated brain histopathological damage in MCAO rats. It also reduced the levels of four inflammatory mediators including IL-1ß (by 70%), IL-6 (by 78%), TNF-α (by 60%) and MCP-1 (by 58%); inhibited microglia and astrocyte activation; and decreased protein expression of iNOS and COX-2 in injured brains. Moreover, PTH down-regulated the protein expressions of TLR4, MyD88, and TRAF6; reduced the expression and nuclear translocation of NF-κB; and lowered the protein expressions of p-ERK1/2, p-JNK, and p-p38. Similar effects were observed in MCAO rats with TAK-242 treatment. However, combined administration of PTH and TAK-242 did not significantly reinforce the anti-inflammatory effects of PTH. DISCUSSION AND CONCLUSION: PTH improved cerebral ischaemia-reperfusion injury by inhibiting neuroinflammation partly via the TLR4/NF-κB/MAPK signalling pathway, which will help guide its clinical application.

Quantification and discovery of quality control chemical markers for Ba-Bao-Dan by UPLC-MS/MS combined with chemometrics.

Ba-Bao-Dan (BBD) is a well-known Traditional Chinese medicine (TCM) prescription in China. It was first formulated in approximately 1555 AD. As one of the National Protected TCM, it is widely used to treat jaundice, viral hepatitis, cholecystitis, acute urinary tract infection, cancer, and other diseases. It is a healthcare medicine that is used to prevent many diseases in China. In other Asian countries and in European and American countries, BBD is used as a drug to protect the liver. However, a systematic quality study on BBD chemical markers has not been carried out. This study aimed to establish an ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) method for the quantitative determination of 43 compounds in BBD. Furthermore, the method was used to further find chemical markers for quality control through the combination with chemometrics. The modified chromatographic conditions were achieved on Waters Cortecs C18 column (2.1 × 100 mm, 1.6 µm) with a gradient elution consisting of 0.1 % formic acid in water and acetonitrile with methanol (1:1, V/V). All analytes were determined in the multiple reaction monitoring mode. The method was validated for linearity, detection limits, precision, repeatability, stability and accuracy. The method was used to analyze the 43 compounds in 11 batches of BBD samples. Hierarchical cluster analysis and principal component analysis were applied to evaluate intrinsic quality of BBD and to identify the potential chemical markers for quality control. In conclusion, the method rapidly and sensitively determined the 43 compounds, among which 10 compounds, namely, N-Gin R1, Gin Re, Gin Rg1, Gin Rb1, GCA, Gin Rd, CA, TCA, CDCA, and DCA, were considered as the potential chemical markers for BBD quality control.

Pien-Tze-Huang, a Chinese patent formula, attenuates NLRP3 inflammasome-related neuroinflammation by enhancing autophagy via the AMPK/mTOR/ULK1 signaling pathway.

NLRP3 inflammasome is a key mediator in ischemic stroke-induced neuroinflammation and subsequent brain injury. Our previous study demonstrated the potent activity of Pien-Tze-Huang (PTH), a well-known Chinese patent formula, in reducing mitochondria-mediated neuronal apoptosis in cerebral ischemia/reperfusion impaired rats. This study aims to elucidate the mechanistic action of PTH related to neuroinflammation in LPS-induced BV2 microglial cells and cerebral ischemia/reperfusion impaired rats. BV2 cells were stimulated with LPS for 12 h and treated with PTH with various concentrations. Modulation by PTH of relevant genes (IL-6, IL-1ß, IL-18, TNF-α, COX-2 and iNOS mRNA) and proteins (NLRP3 inflammasome, autophagy and AMPK/mTOR/ULK signaling) was analyzed by real-time PCR and western blot, respectively. Similar analyses were conducted in middle cerebral artery occlusion rat model including neurological deficit, infarct volume, microglial activation, and key genes and proteins in modulating autophagy and NLRP3. Our results showed that PTH significantly inhibited the production of key proinflammatory mediators and protein expressions of NLRP3 and caspase-1 p20 in LPS induced BV2 cells. It also enhanced the autophagy response by modulating the key autophagy proteins via AMPK/mTOR/ULK related pathway. The reduced inflammatory responses and NLRP3 expressions by PTH were partially blocked by the autophagy inhibitor (3-MA) and AMPK blocker (compound C). In rats, PTH significantly reduced infarct size, suppressed microglial activation, and improved neuron deficit. It also promoted autophagy and reduced NLRP3 activity. Our study demonstrated that PTH inhibited NLRP3 inflammasome-mediated neuroinflammation, which was associated with enhanced autophagy via AMPK/mTOR/ULK1 pathway in vitro and in vivo.

[Effect of fucoxanthin on insulin resistance in obese mice induced by high fat diet].

The aim of this paper was to study the effect and mechanism of fucoxanthin on insulin resistance of obese mice induced by high-fat diet. Fifty C57 BL/6 J male mice were randomly divided into control group and high-fat diet group. The insulin resistance model was induced with high-fat diet for 12 weeks, and model mice were randomly divided into model group, fucoxanthin-0.2% group, fucoxanthin-0.4% group and metformin group. After dietary treatment for 6 weeks, the body weight and epididymal fat weight in each group were measured. Fasting blood glucose(FBG), fasting insulin(FINS), total cholesterol(TC), triglyceride(TG), low-density lipoprotein(LDL-C) and high-density lipoprotein(HDL-C) were measured, and insulin resistance index(HOMA-IR) was calcula-ted. The pathological morphology in liver was observed by hematoxylin eosin staining, and the expressions of some key proteins in insulin receptor substrate 1(IRS-1)/posphoinositide 3-kinase(PI3 K)/serine-threonine kinase(Akt) and peroxisome proliferators-activated receptor-γ(PPARγ)/sterol regulatory element binding protein-1(SREBP-1)/fatty acid synthetase(FAS) pathways in liver were detected by Western blot. According to the findings, compared with the model group, levels of body weight, epididymal fat weight, FBG, FINS, TC, TG, LDL-C and HOMA-IR, as well as protein expressions of PPARγ, SREBP-1 and FAS in liver were significantly reduced(P<0.05 or P<0.01), while level of HDL-C and protein expressions of p-IRS-1, IRS-1, PI3 K and p-Akt in liver were signi-ficantly increased after treatment with fucoxanthin(P<0.05 or P<0.01). And the pathological changes of liver tissue in fucoxanthin-treated mice were also improved obviously. The results showed that fucoxanthin could improve obesity, hyperglycemia and hyperlipidemia, and alleviate insulin resistance in obese mice, and its mechanism is possibly related to the regulation of IRS-1/PI3 K/Akt and PPARγ/SREBP-1/FAS pathways.

Alismatis Rhizoma Triterpenes Alleviate High-Fat Diet-Induced Insulin Resistance in Skeletal Muscle of Mice.

Alismatis rhizoma (AR), which is the dried rhizome of Alisma orientale (Sam.) Juz. (Alismataceae), is an important component of many famous Chinese formulas for hypoglycemic. This study aimed to evaluate the insulin resistance (IR) alleviating effects of AR triterpenes (ART) and ART component compatibility (ARTC, the mixture of 16-oxo-alisol A, 16-oxo-alisol A 23-acetate, 16-oxo-alisol A 24-acetate, alisol C, alisol C 23-acetate, alisol L, alisol A, alisol A 23-acetate, alisol A 24-acetate, alisol L 23-acetate, alisol B, alisol B 23-acetate, 11-deoxy-alisol B and 11-deoxy-alisol B 23-acetate) in high-fat diet-induced IR mice and plamitate-treated IR C2C12 cells, respectively. A dose of 200 mg/kg of ART was orally administered to IR mice, and different doses (25, 50, and 100 µg/ml) of ARTC groups were treated to IR C2C12 cells. IPGTT, IPITT, body weight, Hb1AC, FFA, TNF-α, MCP-1, and IR-associated gene expression (p-AMPK, p-IRS-1, PI3K, p-AKT, p-JNK, and GLUT4) were measured in IR mice. Glucose uptake, TNF-α, MCP-1, and IR-associated gene expression were also measured in IR C2C12 cells. Results showed that ART alleviated high-fat diet-induced IR in the skeletal muscle of mice, and this finding was further validated by ARTC. This study demonstrated that ART presented a notable IR alleviating effect by regulating IR-associated gene expression, and triterpenes were the material basis for the IR alleviating activity of AR.

Anti-osteoporotic effects of alisol C 23-acetate via osteoclastogenesis inhibition.

Alismatis rhizoma (AR) is the dried rhizome of Alisma orientale (Sam.) Juz. (Alismataceae). This traditional Chinese formula is diuretic, hypoglycemic, and hypolipidemic. Alisol C 23-acetate (AC23A) from AR is anti-inflammatory and ameliorates certain metabolic diseases. However, the mechanism by which AC23A mitigates osteoporosis is unknown. The present study investigated the anti-osteoporotic effects of AC23A in vivo and in vitro. In an ovariectomized (OVX) rat model, AC23A ameliorated OVX-induced organ coefficients and trabecular bone loss. In OVX rats, AC23A treatment lowered serum TRAP5b, CTK, ß-CTX, TNF-α, IL-6, and IL-1ß, raised serum E2, and did not significantly change serum OCN or BALP. AC23A inhibited osteoclast formation in a rat co-culture system without affecting osteoblast activity. RANK (receptor activator of nuclear factor kappaB) signaling channels are vital osteoclastogenesis transcription elements. AC23A inhibited RANK ligand (RANKL)-induced TRAP, c-Fos, MMP9, NFATc1, and CTK expression and JNK phosphorylation. Therefore, AC23A is anti-osteoclastogenic in vitro and in vivo by inhibiting RANKL-induced osteoclast differentiation and function. Moreover, AC23A could help prevent or limit osteoclast-mediated bone diseases by inhibiting osteoclastogenesis.

Qualitative and quantitative analysis of phenolic compounds by UPLC-MS/MS and biological activities of Pholidota chinensis Lindl.

Pholidota chinensis Lindl. is commonly used as functional tea or folk medicine in China, but few studies have been conducted on its phenolic composition and bioactivities. This study was aimed to investigate the phenolic profiles of P. chinensis extracts by different solvents (petroleum ether, ethyl acetate, n-butanol and water) and their in vitro antioxidant, antidiabetic, and anti-inflammatory activities. The results showed that a total of 42 phenolic compounds were accurately identified, 30 of them were further quantified in P. chinensis extracts by UPLC-MS/MS. Among four extracts, ethyl acetate extract not only had the highest contents of total phenolics and 21 individual phenolic compounds, but also possessed the strongest antioxidant (DPPH, 1.43 mmol AAE/g; ABTS, 5.38 mmol TE/g; FRAP, 2.58 mmol FSHE/g), α-glucosidase inhibition (13.29 mmol ACAE/g) and anti-inflammation (IC50 = 18.71 µg/ml) activities. Also, the antioxidant, antidiabetic, and anti-inflammatory activities were significantly correlated with total phenolics and individual phenolic compounds. Orientin and vitexin can be considered as the potential quality markers of P. chinensis. This study will provide a comprehensive phenolic profile of P. chinensis and relates them to their antioxidant, antidiabetic, and anti-inflammatory activities.

Bioactive platycodins from Platycodonis Radix: Phytochemistry, pharmacological activities, toxicology and pharmacokinetics.

Platycodonis Radix, the root of Platycodon grandiflorum (Jacq.) A. DC., is a well-known edible herbal medicine. It is a common vegetable used for the preparation of side dish, kimchi, dessert, and tea. Besides, it has been used to treat respiratory disease including cough, excessive phlegm, and sore throat for a long history. In the past decades, the bioactive components and the pharmacological activities of Platycodonis Radix have been widely investigated. Thereinto, platycodins, the oleanane-type triterpenoid saponins were demonstrated to be the main bioactive components in Platycodonis Radix, and more than 70 platycodins have been identified up to date. This paper mainly reviewed the phytochemistry, pharmacological activities (apophlegmatic, anti-tussive, anti-inflammatory, anti-cancer, anti-obesity, anti-diabetic, immunomodulatory, cardiovascular protective, and hepatoprotective activities, etc.), toxicology and pharmacokinetics of platycodins isolated from Platycodonis Radix, aiming to promote further investigation on therapeutic potential of these platycodins.

Quantitative Analysis of Eight Triterpenoids and Two Sesquiterpenoids in Rhizoma Alismatis by Using UPLC-ESI/APCI-MS/MS and Its Application to Optimisation of Best Harvest Time and Crude Processing Temperature.

Rhizoma Alismatis (RA), widely known as "Ze-Xie" in China, is the tuber of Alisma orientale (Sam.) Juzep (Alismaceae), a Chinese herbal medicine that has been used to treat hyperlipidemia, diabetes, hypertension, dysuria, and inflammation. In this study, a sensitive and reliable method based on an ultra-performance liquid chromatography (UPLC) couple with two ionisation modes, including electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI) tandem mass spectrometry (MS), namely, UPLC-ESI/APCI-MS/MS was developed and validated to simultaneously determine 8 triterpenoids (ESI mode) and 2 sesquiterpenoids (APCI mode) in RA. Ten marker compounds were analysed with a Waters' CORTECS UPLC C18 column (200 mm × 2.1 m, 1.6 µm) and gradient elution with water (contained 0.1% formic) and acetonitrile within 7 min. The established method was validated for linearity, intra- and interday precisions, accuracy, recovery, and stability. The calibration curve for 10 marker compounds showed good linear regression (r > 0.9971). The limits of detection and quantification for analytes were 0.14-1.67 ng/mL and 0.44-5.65 ng/mL, respectively. The relative standard deviations (RSD, %) and accuracy (RE, %) of intra- and interday precisions were less than 3.83% and 1.21% and 3.22% and 1.46%, repeatability and stability for real samples were less than 2.78% and 3.19%, respectively. All recoveries of the 10 marker compounds ranged from 97.24% to 102.49% with RSDs less than 4.05%. The developed method efficiently determined the 10 marker compounds in RA and was subsequently applied to optimise harvest time and crude processing temperature. The result indicated the 90% wilted phase and 70°C (or lower) may be the best harvest time and the processing temperature of RA.

Therapeutic Potential of Pien-Tze-Huang: A Review on Its Chemical Composition, Pharmacology, and Clinical Application.

Pien-Tze-Huang (PTH) is a famous and commonly used traditional Chinese medicine formula in China. It was first formulated by a royal physician of the Ming Dynasty (around 1555 AD). Recently, PTH has attracted attention worldwide due to its beneficial effects against various diseases, especially cancer. This paper systematically reviewed the up-to-date information on its chemical composition, pharmacology, and clinical application. A range of chemical compounds, mainly ginsenosides and bile acids, have been identified and quantified from PTH. Pharmacological studies indicated that PTH has beneficial effects against various cancers, hepatopathy, and ischemic stroke. Furthermore, PTH has been used clinically to treat various diseases in China, such as colorectal cancer, liver cancer, and hepatitis. In summary, PTH is a potential agent with extensive therapeutic effects for the treatment of various diseases. However, the lack of information on the side effects and toxicity of PTH is a non-negligible issue, which needs to be seriously studied in the future.