Iridoid Glycosides Research Articles

Gene cloning and functional analysis of an iridoid oxidase gene in Rehmannia glutinosa

Rehmannia glutinosa is one of the commonly used Chinese herbal medicines, which has activities of heat-clearing,blood-cooling, Yin-nourishing, and body fluid-promoting. Iridoid glycosides are the main bioactive in R. glutinosa. Iridoid oxidase is a key rate-limiting enzyme in the biosynthetic pathway of iridoid glycosides. In this study, an iridoid oxidase gene Rg IO was screened based on the transcriptome data, followed by bioinformatics analysis, expression characteristic detection, and subcellular localization analysis. The results show that the coding region of Rg IO is 1 536 bp, with 511 amino acids encoded, and the molecular weight is about 58 258. 01. The protein sequence of Rg IO contains the conserved domains and motifs of cytochrome P450 oxidases. Rg IO has the highest sequence identities with its ortholog proteins in Striga asiatica, Striga hermonthica, and Centranthera grandiflora and has good sequence identities(77. 28%) with Catharanthus roseus Cr IO. Rg IO shows specific expression in the leaf of R. glutinosa. In response to MeJA induction, the expression of MeJA in leaves and roots after treatment increases by 3. 15 and 1. 3 times at 3 h and 6 h,respectively. The result of subcellular localization shows that Rg IO is distributed in the endoplasmic reticulum. Agrobacterium-mediated transient expression of Rg IO gene in leaves of R. glutinosa makes the content of catalpol increase by 0. 82 times compared with the transient expression of the empty vector. This study provides a key target gene for the molecular regulation and biosynthesis of catalpol in R. glutinosa and lays a foundation for revealing the complete biosynthetic pathway of catalpol.

Pharmacological and Biochemical activities of plantago major L

Throughout human history, natural remedies have been sought to treat diseases. The therapeutic wounds of plants are accepted worldwide as a result of many studies and research. Medicinal plants have started to be used in the pharmaceutical sector due to the chemical compounds contained in their structures. One of the potential plants that can be used in traditional medicine is the broadleaf plantain, white man's footprint, waybread, or greater plantain. Scientifically known as Plantago major, it is a wild plant belonging to the Plantaginaceae family that can reach a height of about 15 cm. Plantago major leaves have been used for centuries almost everywhere in the world as a wound healer and in the treatment of many diseases other than wound healing. Among them are treatments for skin, respiratory organs, digestive organs, reproduction, circulatory diseases, infections, and cancer. It is also used as a decongestant and analgesic. Plantago major contains biologically active compounds such as polysaccharides, lipids, caffeic acid derivatives, flavonoids, iridoid glycosides, and terpenoids. Alkaloids and some organic acids have also been detected. There are several biological activities from plant extracts, including wound healing activity, anti-inflammatory, analgesic, antioxidant, weak antibiotic, immune modulating, and antiulcerogenic activity. The widespread use of Plantago species in food and traditional medicine has attracted the attention of researchers looking for active principles and mechanisms of action. However, more studies are needed to better prove the medical applications, phytochemical properties, and pharmacological properties of this breed.

ANTI-INFLAMMATORY ACTIVITY OF PLANTAGO MAJOR LEAF EXTRACTS IN VITRO ON EPITHELIAL CELLS OF THE ORAL CAVITY

The large plantain has been widely used since ancient times to treat many diseases, including constipation, cough and ulcers. The purpose of this study is to review the traditional use, botanical characteristics, pharmacological activity, phytochemical effects and toxicity of Plantago major. Some o f its traditional properties, including wound healing, antipyretic, antitussive, anti-infective, anti-hemorrhagic, anti-inflammatory, diuretic, laxative, astringent and hemostatic, have been confirmed by recent studies. Phytochemical studies have shown that Plantago major contains volatile compounds, triterpenoids, phenolic acids and flavonoids. Current pharmacological studies have proven some of the traditional uses of Plantago major. However, additional studies of this plant are needed, since it can be used for the production of various natural preparations.The healing properties of the great plantain have been recognized all over the world for hundreds of years. This plant contains a number of effective chemical components, such as flavonoids, alkaloids, terpenoids, phenolic acid derivatives, iridoid glycosides, fatty acids, polysaccharides and vitamins, which contribute to its specific therapeutic effect. Accordingly, studies have shown that the large plantain is effective as a wound healing agent, as well as as an anti-cancer, antidiabetic, antidiarrheal, anti-inflammatory, antinociceptive, antibacterial and antiviral agent. It also fights fatigue and cancer, is an antioxidant and neutralizes free radicals.

Serum albumin exposure enhances cell invasiveness and paclitaxel resistance in human neuroblastoma cells, with attenuation by valeriana-type iridoid glycosides.

Neuroblastoma, a prevalent extracranial solid tumor in children, arises from undifferentiated nerve cells. While tumor vasculature, often characterized by increased permeability, influences metastasis and recurrence, the direct impact of blood-borne molecules on tumor progression remains unclear. In the present study, we focused on the effect of exposure to albumin, one of the most abundant proteins in the serum, on human neuroblastoma cells. Albumin exposure elevated oxidative stress and led to mitochondria dysfunction via the activation of TGFβ and PI3K pathways, accompanied by an increase in the metastatic and invasive properties of neuroblastoma cells. Proteins relevant to the induction of autophagy were upregulated in response to prolonged albumin exposure. Additionally, pre-exposure to albumin before treatment resulted in increased resistance to paclitaxel. Two valeriana-type iridoid glycosides, patrisophoroside and patrinalloside, recently isolated from Nardostachys jatamansi significantly mitigated the effect of albumin on oxidative stress, cell invasiveness, and chemoresistance. These findings illuminate the potential role of blood-borne molecules, such as albumin, in the progression and metastasis of neuroblastoma, as well as the possible therapeutic implications of valeriana-type iridoid glycosides in anti-cancer treatment.

Eremostachys laevigata Bunge responses to different extraction solvents and methods: physiological, biochemical, and antibacterial attributes

This study examined the biochemical composition of Eremostachys laevigata Bunge's aerial and underground organs using various solvents (methanol, water, N-hexane, chloroform, and acetone) and their impact on antibacterial activity against eight bacterial strains (Escherichia coli, Staphylococcus aureus, Salmonella enterica, Pseudomonas aeruginosa, Klebsiella pneumoniae, Shigella dysenteriae, Proteus mirabilis, and Bacillus cereus). Soxhlet and maceration extraction methods were used, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined using the tube dilution method. The study found that N-Hexane and water solvents had the highest total phenol content, while methanol, acetone, and chloroform had the lowest. Additionally, N-Hexane and methanol solvents showed the highest and lowest flavonoid content, respectively. The methanol extract from underground organs using the Soxhlet method exhibited the strongest antibacterial activity, whereas the acetone extract showed the weakest antimicrobial effect. Staphylococcus aureus displayed both the MIC and MBC, and Salmonella enterica showed the highest susceptibility to the well diffusion method, while both Escherichia coli and Staphylococcus aureus were highly susceptible to the disk diffusion method. The underground organs contained 6.87 mg.g-1 of phenolic compounds and 0.19 mg.g-1 of flavonoids. Two iridoid glycosides, pholoyoside and sesamoside, were separated from the methanol extract of the underground organs using reversed-phase HPLC. The research highlights E. laevigata Bunge's potential as a natural reservoir of antimicrobial compounds, with phenolic and flavonoid compounds, along with iridoid glycosides, presumed to contribute to its antibacterial properties.

Comprehensive evaluation of Ixoroside: An iridoid glycoside from Nepeta aristata and N. baytopii, assessing antioxidant, antimicrobial, enzyme inhibitory, DNA protective properties, with computational and pharmacokinetic analyses

Ixoroside, an iridoid glycoside, was isolated from two endemic plants, Nepeta aristata and Nepeta baytopii and its structure was elucidated by comprehensive analysis with NMR and mass spectrophotometers. It was observed that the compound exhibited strong antioxidant activity in phosphomolybdenum-reducing power (55.65±0.02 μg/mL), H2O2 (2.97±0.50 μg/mL), and superoxide anion scavenging (11.31±0.19 μg/mL) activities. It has also been noted that the ixoroside molecule has enzyme inhibitor (7.01±0.001 μg/mL for urease, 19.06±0.51 μg/mL for AChE, 9.90±0.5 μg/mL for BChE, 16.87±0.08 μg/mL for α-amylase, 4.11±0.36 μg/mL for α-glucosidase and 2.23±0.001 μg/mL for tyrosinase) and DNA protective effect (55.14% for Form I) and antibacterial (10 mm against K. pneumoniae, 9.00 mm against E. faecalis and 11.00 mm against S. aureus, 128 μg/mL against E. coli and E. faecalis). In silico studies, density functional theory (DFT) and molecular docking were performed to elucidate ixoroside interaction with enzymes. In enzyme inhibition kinetics, ixoroside exhibited strong interaction with urease (Ki, 0.11 mM, mixed-uncompetitive), α-glucosidase (Ki, 0.10 mM, noncompetitive) and tyrosinase (Ki, 0.10 mM, noncompetitive). Additionally, BChE was observed to interact strongly with α-glucosidase and tyrosinase with binding constants of 0.49, 1.19 and 3.15 μM in molecular docking. Moreover, the pharmacological properties of ixoroside examined by adsorption, distribution, metabolism, excretion and toxicity (ADMET) showed that the molecule has drug-like properties.

A new iridoid glycoside and other secondary metabolites from Sideritis dichotoma Huter and their chemotaxonomic significance

The phytochemical studies on the aerial parts of Sideritis dichotoma led to the isolation and identification of a new iridoid glycoside (1), along with four known iridoid glycosides (2-5), three phenylethanoid glycosides (6–8), two flavone glycosides (9 and 10), one neolignan (11) and a megastigmane glycoside (12). Their structures were elucidated by spectroscopic techniques. Compounds 2, 3 and 12 have never been found in the Sideritis genus before. Furthermore, eleven compounds (1–5, 7–12) were characterized for the first time from S. dichotoma. The chemotaxonomic importance of isolated compounds was discussed. This is the first phytochemical study on the polar constituents of S. dichotoma, an endemic species to Türkiye.

Androsin alleviates non-alcoholic fatty liver disease by activating autophagy and attenuating de novo lipogenesis

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with therapeutic options on the horizon. Picrorhiza kurroa, enriched with iridoid glycosides like picroside I and picroside II is known for its hepatoprotective activity and anti-inflammatory properties. Androsin, the other phytochemical present in P. kurroa has been shown to have anti-inflammatory and anti-asthmatic properties. However, its role in NAFLD is yet to be investigated. PurposeThis study aims to identify the potent hepatoprotective agent from P. kurroa that can attenuate NAFLD in HFrD-fed ApoE−/− mice, and elucidate the underlying mechanisms governing its effects. MethodsClassical purification methods were used to isolate seven compounds, including picroside I, picroside II and androsin from the roots of P. kurroa. NAFLD-induced ApoE−/- mice were administered orally with either picroside I, picroside II, or androsin for 7 weeks. Animals were scanned non-invasively by ultrasonography at 1st and 14th week. Gross histomorphometry was examined by HE and Sirius red staining. mRNA transcript and protein profile associated with autophagy, lipogenesis, inflammation, and fibrosis was done through RT-PCR and Western blot analysis. ResultsIn-vitro and in-vivo studies revealed that among the seven evaluated compounds, androsin shows the most potent in-vitro activity. Oral dosing of androsin (10 mg/kg) protected the liver against HFrD-induced NAFLD in ApoE−/− mice model. Biochemical analysis revealed a reduction in ALT and AST enzymes and a significant reduction in cholesterol levels. Hepatocyte ballooning, hepatic lipid deposition, inflammation, and fibrosis were reduced. Androsin treatment significantly reduced fibrosis (α-SMA, collagens, TGF-β) and inflammation (ILs, TNF-α, NFκB) in ApoE−/− mice. Mechanistically, androsin activated AMPKα and down-regulated the expression of SREBP-1c, resulting in ameliorating hepatic lipogenesis. ConclusionOur results support autophagy as one of the therapeutic strategies to reduce steatosis and hepatic damage. We found that androsin treatment significantly ameliorated hepatic steatosis, serum lipid levels, and hepatic injury in ApoE−/− induced by HFrD. Androsin administration mitigated lipogenesis by inhibiting SREBP1c/FASN pathway and activating autophagy through AMPKα/PI3K/Beclin1/LC3 pathway.

The paradox of Picroside II: As a natural antioxidant, but may instead futher aggravate liver injury by exacerbating mitochondrial oxidative stress.

Picroside II (PII), an iridoid glycoside extracted from the rhizomes and stems of the genus Picroside, exhibits pronounced hepatoprotective properties. Pre-administration of PII protects against acute liver injury caused by D-galactosamine (D-Gal), carbon tetrachloride (CCl4), and acetaminophen (APAP). This study aimed to elucidate the ramifications of PII administration subsequent to the initiation of acute hepatic injury. Exploring the role of PII treatment in APAP-treated cell and rat models and in D-Gal and CCl4-treated rat models. In rats, APAP treatment increased serum aspartate transaminase, alanine transaminase, and alkaline phosphatase levels and decreased glutathione activity and the fluidity of the liver mitochondrial membrane. In L-02 cells, APAP exposure resulted in a decrement in membrane potential, an augmentation in the liberation of reactive oxygen species, and an acceleration of apoptotic processes. Moreover, PII pre-administration protected against D-Gal-induced acute hepatic injury and CCl4-induced chronic hepatic injury in rodent models, whereas PII administration post-injury aggravated CCl4-induced chronic hepatic injury. Our results suggest that the effects of PII depend on the hepatic physiological or pathological state at the time of intervention. While PII possesses the potential to avert drug-induced acute hepatic injury through the mitigation of oxidative stress, its administration post-injury may exacerbate the hepatic damage, underscoring the critical importance of timing in therapeutic interventions.

Deciphering the chemical constituents of Phlomis monocephala extracts using UHPLC-HRMS and their antioxidant, neuroprotective, antidiabetic and toxic potentials

In the current study, five different extracts (n-hexane, ethyl acetate, dichloromethane, ethanol, and water) of Phlomis monocephala were analyzed for the first time by ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) to identify their phenolic compounds. The extracts were also evaluated for their non-enzyme antioxidant activities using a variety of methods, including DPPH and, ABTS•+ scavenging activities, reduction of ferric (Fe3+), and cupric ions (Cu2+), metal chelating (MCA) activities, and phosphomolybdenum (PBD). Additionally, the extracts were assessed for their in vitro enzyme inhibition potential (acetylcholinesterase (AChE)/butyrylcholinesterase (BChE), α-amylase, α-glucosidase, and tyrosinase). Furthermore, cell viability was evaluated on HepG2 (human hepatocellular carcinoma), S17 cells (murine bone marrow stromal) and RAW (murine macrophages). UHPLC-HRMS allowed for the identification of 115 compounds from different chemical groups including flavonoids, iridoid glycosides, phenylethanoid glycosides and others. Most of the extracts had strong antioxidant potential and were rich in phenolic compounds. Ethanol and water extracts appear as the most promising antioxidant extracts providing the highest values followed by ethyl acetate by all the methodologies employed in this study. Furthermore, all the extracts, except the aqueous extract, inhibited all the enzymes significantly. Surprisingly, the aqueous extract did not show a prominent inhibition (low or no inhibition) against these enzymes. Hexane, ethyl acetate, and dichloromethane exhibited extremely significant cytotoxic effects against all cell lines at a higher concentration. The HepG2 cells demonstrated lower sensitivity to the extracts than RAW and S17 cells. In conclusion, P. monocephala can be considered as a valuable ingredient for the production of functional applications including nutraceuticals.

Natural products from Odontonema strictum promote neurite outgrowth in neuronal PC12 cells

The leaves of Odontonema strictum, a tropical plant used for its antihypertensive properties, are rich in nutrients and biologically active phytochemicals, such as β-sitosterol, stigmasterol, umuravumbolide, deacetylumuravumbolide, dideacetylboronolide, deacetylboronolide, verbascoside, and isoverbascoside. In addition, its roots are rich in β-sitosterol, stigmasterol, and the iridoid glycoside β-O-methyl-unedoside. Ingestion of the roots was reported to have a sedative effect in a dog was previously reported on a dog eating the roots of this plant. In the present study, we report for the first time the cell proliferation- and neurite outgrowth-promoting effects in PC12 neuronal cells of the isolated organic compounds and crude extracts from O. strictum. Pituitary adenylate cyclase-activating peptide (PACAP) and quercetin were used as positive controls. At the concentration of 0.2 μg/mL, β-sitosterol was more potent than quercetin and displayed the same activity (>45 μm/cell) as PACAP (100 nM). At a low concentration (0.04 μg/mL), verbascoside and isoverbascoside showed the strongest neurite outgrowth-promoting effect (neurite length of 30 to 35 μm/cell). Our results indicate that phytomedicines made from O. strictum may be useful in preventing neurodegenerative diseases.

Geniposide Attenuates Oxygen-glucose Deprivation/Recovery-induced Retinal Ganglion Cell Injury via Akt/Nrf-2 Signaling Pathway.

Glaucoma is an eye disease. Its pathological process involves retinal ischemia-reperfusion (I/R), which causes irreversible blindness in patients. Geniposide (Gen), a bioactive iridoid glycoside extracted from the fruit of gardenia, exhibits many biological effects, such as anti-oxidative stress, anti-inflammation, anti-apoptosis, anti-endoplasmic reticulum stress, and anti-thrombotic effects. However, its therapeutic potential for the retinal I/R injury remains unclear. This study investigated the protective effect of Gen against I/R injury by inhibiting abnormal reactive oxygen species (ROS) and retinal neuron apoptosis. We used oxygen-glucose deprivation/reoxygenation (OGD/R) to induce R28 cells to mimic the pathological process of I/R in glaucoma. We conducted CCK-8 analysis and TUNEL staining to examine cell proliferation and apoptosis in glaucoma. Western blotting was used to assay the expressions of apoptosis and Akt/Nrf-2 pathway-related proteins. The production of ROS was detected by using the corresponding kit. Cell viability decreased, whereas TUNEL staining-positive cells and ROS production increased after the OGD/R injury. The contents of cleaved caspase-3 and Bax/Bcl-2 increased after the OGD/R injury. Treatment with 200 μM of Gen effectively improved the cell viability and suppressed cell apoptosis and ROS production. In addition, Gen could significantly promote the activation of the Akt/Nrf-2 signaling pathway in R28 cells, which was blocked by the inhibition of Akt/Nrf-2. We in vivo verified the neuroprotective effect of Gen by establishing an acute high intraocular pressure (aHIOP) model and obtained similar results to those of the in vitro experimental results. Hence, it can be suggested that Gen provides neuroprotection against the OGD/R-induced injury of R28 cells by activating the Akt/Nrf-2 signaling pathway, which is beneficial for the clinical treatment of glaucoma.

Metabolome-microbiome insights into therapeutic impact of 8-O-acetylharpagide against breast cancer in a murine model.

Iridoid glycosides extract, which is the main active extract of Ajuga decumbens Thunb, has been proved to have anti-breast cancer activity in previous studies. However, it is still unknown whether 8-O-acetylharpagide, a main active compound in the extract, has anti-breast cancer activity. In this study, 4T1 breast cancer mice model was first successfully established. Then the anti-breast cancer effect of 8-O-acetylharpagide was systematically investigated. Feces were collected for metabolomics and 16S rRNA analysis to assess the potential mechanism. The results showed that 8-O-acetylharpagide was effective in reducing 4T1 mouse tumor volume and weight compared with the model group. Metabolome analysis revealed 12 potential metabolite biomarkers in feces, mainly involved in primary bile acid biosynthesis and arachidonic acid metabolism. The 16S rRNA sequencing results demonstrated that 8-O-acetylharpagide modulated the abundance of the intestinal flora in 4T1 mice. Spearman correlation analysis showed that calcitriol and prostaglandin G2 strongly correlated with Akkermansia, Firmicutes and Muribaculum. Overall, the active compound 8-O-acetylharpagide could inhibit significantly breast cancer growth in 4T1 breast cancer model mice. The mechanism of the anti-breast cancer effect of 8-O-acetylharpagide may be related to the regulation of primary bile acid biosynthesis and arachidonic acid metabolism and modulation of the abundance of Akkermansia and Firmicutes.

Shining insights: Deciphering the biogenic synthesis of Ajuga bracteosa-mediated gold nanoparticles with advanced microscopy techniques.

In this study, gold nanoparticles (AuNPs) were bioreduced from Ajuga bracteosa, a medicinal herb known for its therapeutic properties against various diseases. Different fractions of the plant extract were used, including the methanolic fraction (ABMF), the n-hexane fraction (ABHF), the chloroform fraction (ABCF), and the aqueous extract for AuNPs synthesis. The characterization of AuNPs was performed using UV-Vis spectrophotometry, FT-IR, XRD, EDX, and TEM. UV-Vis spectroscopy confirmed the formation of AuNPs, with peaks observed at 555 nm. FT-IR analysis indicated strong capping of phytochemicals on the surface of AuNPs, which was supported by higher total phenolic contents (TPC) and total flavonoid contents (TFC) in AuNPs. XRD results showed high crystallinity and a smaller size distribution of AuNPs. TEM analysis revealed the spherical shape of AuNPs, with an average size of 29 ± 10 nm. The biologically synthesized AuNPs exhibited superior antibacterial, antioxidant, and cytotoxic activities compared to the plant extract fractions. The presence of active biomolecules in A. bracteosa, such as neoclerodan flavonol glycosides, diterpenoids, phytoecdysone, and iridoid glycosides, contributed to the enhanced biological activities of AuNPs. Overall, this research highlights the potential of A. bracteosa-derived AuNPs for various biomedical applications due to their remarkable therapeutic properties and effective capping by phytochemicals. RESEARCH HIGHLIGHTS: This research underscores the growing significance of herbal medicine in contemporary healthcare by exploring the therapeutic potential of Ajuga bracteosa and gold nanoparticles (AuNPs). The study highlights the notable efficacy of A. bracteosa leaf extracts and AuNPs in treating bacterial infections, demonstrating their bactericidal effects on a range of strains. The anti-inflammatory properties of plant extracts and nanoparticles are evidenced through paw edema method suggesting their applicability in managing inflammatory conditions. These findings position A. bracteosa and AuNPs as potential candidates for alternative and effective approaches to modern medication.

A Review of Iridoid Glycosides Content and Their Biological Properties from Genus Citharexylum

A Review of Iridoid Glycosides Content and Their Biological Properties from Genus Citharexylum

Optimization of extracting technology of iridoid glycosides and phenylethanoid glycosides from Pedicularis decora Franch. by G1-entropy-coupled response surface methodology and rapid identification by UPLC-Q/TOF-MS

Quality control and clarifying ingredients are the foundation of pharmacodynamic material basis research. Pedicularis decora Franch. (P. decora) is clinically used to treat Alzheimer’s disease and exerts significant antioxidative, anti-inflammatory and neuroprotective effects. However, there is little systematic research on the extraction and composition and the current research on P. decora focused on the quality control and extraction with aucubin as only quality marker. It reported that Iridoid glycosides (IGs) and phenylpropanoid glycosides (PeGs), which are characteristic components of the Pedicularis species, have been reported to have various anti-Alzheimer’s activity. This study focused on the extraction and rapid qualitative analysis of IGs and PeGs in P. decora. First, HPLC-UV method was established to detect five IGs and PeGs analytes simultaneously and assess the effect of the extraction technology. Then, the G1-entropy method with the Box-Behnken response surface design methodology was used to optimized extraction technology. The optimum conditions were determined to be reflux with 55% methanol aqueous solutions, at 75 °C for 50 min. Finally, by establishing UPLC-Q/TOF-MS, 15 IGs and 15 PeGs in P. decora were rapidly identified and characterized for the first time. The results will provide a reverence of a higher quality standard and the pharmacodynamic material basis research.

Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress.

Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis, is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H2O2) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H2O2-induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H2O2-challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H2O2-induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H2O2-mediated calcium (Ca2+) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca2+-dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca2+-mediated ER stress by minimizing oxidative stress, thereby inhibiting H2O2-induced cytotoxicity in C2C12 myoblasts.

Geniposide ameliorates atherosclerosis by restoring lipophagy via suppressing PARP1/PI3K/AKT signaling pathway

BackgroundAtherosclerosis (AS) is the leading cause of global death, which manifests as arterial lipid stack and plaque formation. Geniposide is an iridoid glycoside extract from Gardenia jasminoides J.Ellis that ameliorates AS by mediating autophagy. However, how Geniposide regulates autophagy and treats AS remains unclear. PurposeTo evaluate the efficacy and mechanism of Geniposide in treating AS.Study design and methods: Geniposide was administered to high-fat diet-fed ApoE−/− mice and oxidized low-density lipoprotein-incubated primary vascular smooth muscle cells (VSMCs). AS was evaluated with arterial lipid stack, plaque progression, and collagen loss in the artery. Foam cell formation was detected by lipid accumulation, inflammation, apoptosis, and the expression of foam cell markers. The mechanism of Geniposide in treating AS was assessed using network pharmacology. Lipophagy was measured by lysosomal activity, expression of lipophagy markers, and the co-localization of lipids and lipophagy markers. The effects of lipophagy were blocked using Chloroquine. The role of PARP1 was assessed by Olaparib (a PARP1 inhibitor) intervention and PARP1 overexpression. ResultsIn vivo, Geniposide reversed high-fat diet-induced hyperlipidemia, plaque progression, and inflammation. In vitro, Geniposide inhibited VSMC-derived foam cell formation by suppressing lipid stack, apoptosis, and the expressions of foam cell markers. Network pharmacological analysis and in vitro validation suggested that Geniposide treated AS by enhancing lipophagy via suppressing the PI3K/AKT signaling pathway. The benefits of Geniposide in alleviating AS were offset by Chloroquine in vivo and in vitro. Inhibiting PARP1 using Olaparib promoted lipophagy and alleviated AS progression, while PARP1 overexpression exacerbated foam cell formation and lipophagy blockage. The above effects of PARP1 were weakened by PI3K inhibitor LY294002. PARP1 also inhibited the combination of the ABCG1 and PLIN1. ConclusionGeniposide alleviated AS by restoring PARP1/PI3K/AKT signaling pathway-suppressed lipophagy. This study is the first to present the lipophagy-inducing effect of Geniposide and the binding of ABCG1 and PLIN1 inhibited by PARP1.

Urease and human glioblastoma (U87) cells growth inhibitory iridoid glycoside acetates from Nyctanthes arbor-tristis Linn.

The present study was undertaken on the chemical constituents of ethanol extract of aerial parts of Nyctanthes arbor-tristis Linn., and their determination of growth inhibitory activity against glioblastoma multiforme cell line (U87) and urease inhibitory activity. Six constituents were isolated including two new arbortristoside F tetraacetate (1) and arbortristoside G heptaacetate (2) and four known arborside A tetraacetate (3), arborside C pentaacetate (4), 6,7-di-O-acetyl-6β-hydroxyloganin hexaacetate (5) and nyctanthoside heptaacetate (6) iridoid glycoside acetates. Their structures were elucidated using spectroscopic methods, including 1D and 2D NMR and mass analyses. Compounds 3 and 6 showed significant growth inhibition of U87 cell line (76.41 and 87.62% inhibition) respectively while 2, 4 and 5 showed moderate inhibition. 3 and 6 showed notable urease inhibition (IC50 = 17.2 ± 0.4 and 17.2 ± 0.7 µM) respectively, and IC50 of 2, 4 and 5 were 23.8 − 56.3 µM. Compound 1 was inactive.

Chemical constituents of the aerial parts of Mitracarpus hirtus (L.) DC (Rubiaceae)

A phytochemical investigation of the aerial parts of Mitracarpus hirtus afforded thirteen compounds, including a new naphthoquinone di-glycoside (1), three isopentenyl isoflavones (2−4), four flavonoids (5−8), three iridoid glycosides (9 − 11) and two coumarins (12 and 13). Their structures were elucidated based on extensive spectroscopic analyses, chemical methods, and the comparison with the literature. Among them, compound 1 possesses a 2-(3-methylnaphthalen-2-yl)acetic acid core with two glucosyl groups, compounds 2−4 are the first three representatives from the Rubiaceae family, and compounds 9−11 and 13 were isolated from Mitracarpus genus for the first time. Additionally, compounds 2−4 displayed potent antibacterial activities against Helicobacter pylori G27/HP159/JRES00015 (MIC = 4–16 μg/mL) , comparable to metronidazole. To date, wighteone (2) is the most active isoflavone with favourable predicted ADMET properties reported against H. pylori.