Bioactivities of morroniside: A comprehensive review of pharmacological properties and molecular mechanisms.

Morroniside (MOR) is an iridoid glycoside and the main active principle of the medicinal plant, Cornus officinalis Sieb. This phytochemical is associated with numerous health benefits due to its antioxidant properties. The primary objective of the present study was to assess the pharmacological effects and underlying mechanisms of MOR, utilizing published data obtained from literature databases. Data collection involved accessing various sources, including PubMed/Medline, Scopus, Science Direct, Google Scholar, Web of Science, and SpringerLink. Our findings demonstrate that MOR can be utilized for the treatment of several diseases and disorders, as numerous studies have revealed its significant therapeutic activities. These activities encompass anti-inflammatory, antidiabetic, lipid-lowering capability, anticancer, trichogenic, hepatoprotective, gastroprotective, osteoprotective, renoprotective, and cardioprotective effects. MOR has also shown promising benefits against various neurological ailments, including Alzheimer's disease, Parkinson's disease, spinal cord injury, cerebral ischemia, and neuropathic pain. Considering these therapeutic features, MOR holds promise as a lead compound for the treatment of various ailments and disorders. However, further comprehensive preclinical and clinical trials are required to establish MOR as an effective and reliable therapeutic agent.

Total iridoid glycoside extract of Lamiophlomis rotata (Benth) Kudo accelerates diabetic wound healing by the NRF2/COX2 axis.

BACKGROUND: Lamiophlomis rotata (Benth.) Kudo (L. rotata), the oral Traditional Tibetan herbal medicine, is adopted for treating knife and gun wounds for a long time. As previously demonstrated, total iridoid glycoside extract of L. rotata (IGLR) induced polarization of M2 macrophage to speed up wound healing. In diabetic wounds, high levels inflammatory and chemotactic factors are usually related to high reactive oxygen species (ROS) levels. As a ROS target gene, nuclear factor erythroid 2-related factor 2 (NRF2), influences the differentiation of monocytes to M1/M2 macrophages. Fortunately, iridoid glycosides are naturally occurring active compounds that can be used as the oxygen radical scavenger. Nevertheless, the influence of IGLR in diabetic wound healing and its associated mechanism is largely unclear. MATERIALS AND METHODS: With macrophages and dermal fibroblasts in vitro, as well as a thickness excision model of db/db mouse in vivo, the role of IGLR in diabetic wound healing and the probable mechanism of the action were investigated. RESULTS: Our results showed that IGLR suppressed oxidative distress and inflammation partly through the NRF2/cyclooxygenase2 (COX2) signaling pathway in vitro. The intercellular communication between macrophages and dermal fibroblasts was investigated by the conditioned medium (CM) of IGLR treatment cells. The CM increased the transcription and translation of collagen I (COL1A1) and alpha smooth muscle actin (α-SMA) within fibroblasts. With diabetic wound mice, the data demonstrated IGLR activated the NRF2/KEAP1 signaling and the downstream targets of the pathway, inhibited COX2/PEG2 signaling and decreased the interaction inflammatory targets of the axis, like interleukin-1beta (IL-1ß), interleukin 6 (IL-6), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase1 (caspase1) and NOD-like receptor-containing protein 3 (NLRP3).In addition, the deposition of COL1A1, and the level of α-SMA, and Transforming growth factor-ß1 (TGF-ß1) obviously elevated, whereas that of pro-inflammatory factors reduced in the diabetic wound tissue with IGLR treatment. CONCLUSION: IGLR suppressed oxidative distress and inflammation mainly through NRF2/COX2 axis, thus promoting paracrine and accelerating wound healing in diabetes mice.

In silico Molecular Docking Approach to Identify Potential Antihypertensive Compounds from Ajuga integrifolia Buch.-Ham. Ex D. Don (Armagusa).

Background: Ajuga integrifolia (Armagusa) is used as a decoction to treat high blood pressure and diabetes, widely in Ethiopia. Specific compounds for anti-hypertension activity were not identified so far. This study aims to provide a scientific basis for the therapeutic use of A. integrifolia as an antihypertension agent. Methods: In silico studies were used to evaluate the antihypertensive components of A. integrifolia. Flavonoids identified using HPLC analysis and iridoid glycosides isolated from A. integrifolia in this study and those isolated from synonyms (A. remota and A. bractosa) were considered in the molecular docking study. Interactions were studied by using Autodock vina (1.2) on PyRx 0.8 and visualizing in 2D and 3D using ligPlot+ and Discovery studio software. Activities like vasoprotection and druglikeness properties were predicted using online servers. Results: Flavonoids such as quercetin, myricetin, and rutin were identified and quantified by HPLC analysis from different extracts of A. integrifolia. Reptoside and 8-O-acetylharpgide isolated from the aerial part of A. integrifolia. The binding energies of all 17 candidates considered in this study range from -10.2 kcal/mol to -7.5 kcal/mol and are lower than enalapril (reference drug: -5.9 kcal/mol). The binding energies, in most case, constitute hydrogen bonding. Biological activity predicted using PASS test also showed that the flavonoids have more probability of activity than the iridoid glycosides. Druglikeness properties of the candidate molecules showed that most follow the Lipinski rule of five with few violations. Conclusion: Lower binding energies involving hydrogen bonding and predicted activities concerning hypertension confirm the traditional use of the aerial part of the medicinal plant concerned. Flavonoids: rutin, myricetin, quercetin, and kaempferol take the leading role in the antihypertensive activity of the aerial part of A. integrifolia. The iridoid glycosides studied are almost similar in their effect on their antihypertensive activity and still better than the reference drug.

Investigating the mechanism of cornel iridoid glycosides on type 2 diabetes mellitus using serum and urine metabolites in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornel iridoid glycosides (CIG) are extracted from Corni fructus, a herbal medicine used in traditional Chinese medicine to treat diabetes. However, the antidiabetic effects of CIG and the underlying metabolic mechanisms require further exploration. AIM OF THE STUDY: This study aimed to assess the antidiabetic effects and metabolic mechanism of CIG by performing metabolomic analyses of serum and urine samples of rats. MATERIALS AND METHODS: A rat model of type 2 diabetes mellitus (T2DM) was established by administering a low dose of streptozotocin (30 mg/kg) intraperitoneally after 4 weeks of feeding a high-fat diet. The model was evaluated based on several parameters, including fasting blood glucose (FBG), random blood glucose (RBG), urine volume, liver index, body weight, histopathological sections, and serum biochemical parameters. Subsequently, serum and urine metabolomics were analyzed using ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS). Data were analyzed using unsupervised principal component analysis (PCA) and supervised orthogonal partial least squares discriminant analysis (OPLS-DA). Differential metabolites were examined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways to explore the underlying mechanisms. RESULTS: After 4 weeks of treatment with different doses of CIG, varying degrees of antidiabetic effects were observed, along with reduced liver and pancreatic injury, and improved oxidative stress levels. Compared with the T2DM group, 19 and 23 differential metabolites were detected in the serum and urine of the CIG treatment group, respectively. The key metabolites involved in pathway regulation include taurine, chenodeoxycholic acid, glycocholic acid, and L-tyrosine in the serum and glycine, hippuric acid, phenylacetylglycine, citric acid, and D-glucuronic acid in the urine, which are related to lipid, amino acid, energy, and carbohydrate metabolism. CONCLUSIONS: This study confirmed the antidiabetic effects of CIG and revealed that CIG effectively controlled metabolic disorders in T2DM rats. This seems to be meaningful for the clinical application of CIG, and can benefit further studies on CIG mechanism.

[UPLC-Q-TOF-MS-based metabolomics reveals mechanism of Morinda officinalis iridoid glycosides in treating rheumatoid arthritis and bone loss].

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides(MOIG) on paw edema and bone loss of rheumatoid arthritis(RA) rats, and analyze its potential mechanism based on ultra-high performance liguid chromatography-guadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) serum metabolomics. RA rats were established by injecting bovin type Ⅱ collagen. The collagen-induced arthritis(CIA) rats were administered drug by gavage for 8 weeks, the arthritic score were used to evaluate the severity of paw edem, serum bone metabolism biochemical parameters were measured by ELISA kits, Masson staining was used to observe the bone microstructure of the femur in CIA rats. UPLC-Q-TOF-MS was used to analyze the alteration of serum metabolite of CIA rats, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to screen the potential biomarkers, KEGG database analysis were used to construct related metabolic pathways. The results demonstrated that the arthritic score, serum levels of IL-6 and parameters related with bone metabolism including OCN, CTX-Ⅰ, DPD and TRAP were significantly increased, and the ratio of OPG and RANKL was significantly decreased, the microstructure of bone tissue and cartilage were destructed in CIA rats, while MOIG treatments could significantly reduce arthritis score, mitigate the paw edema, reverse the changes of serum biochemical indicators related with bone metabolism, and improve the microstructure of bone tissue and cartilage of CIA rats. The non-targeted metabolomics results showed that 24 altered metabolites were identified in serum of CIA rats; compared with normal group, 13 significantly altered metabolites related to RA were identified in serum of CIA rats, mainly involving alanine, aspartate and glutamate metabolism; compared with CIA model group, MOIG treatment reversed the alteration of 15 differential metabolites, mainly involving into alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis. Therefore, MOIG significantly alleviated paw edema, improved the destruction of microstructure of bone and cartilage in CIA rats maybe through involving into the regulation of amino acid metabolism.

Therapeutic potentials of iridoids derived from Rubiaceae against in vitro and in vivo inflammation: A scoping review.

Acute inflammation may develop into chronic, life-threatening inflammation-related diseases if left untreated or if there are persistent triggering factors. Cancer, diabetes mellitus, stroke, cardiovascular diseases, and neurodegenerative disorders are some of the inflammation-related diseases affecting millions of people worldwide. Despite that, conventional medical therapy such as non-steroidal anti-inflammatory drugs (NSAIDs) is associated with serious adverse effects; hence, there is an urgent need for a newer and safer therapeutic alternative from natural sources. Iridoids are naturally occurring heterocyclic monoterpenoids commonly found in Rubiaceae plants. Plant extracts from the Rubiaceae family were demonstrated to have medicinal benefits against neurodegeneration, inflammation, oxidative stress, hyperglycaemia, and cancer. However, the therapeutic effects of natural iridoids derived from Rubiaceae as well as their prospective impacts on inflammation in vitro and in vivo have not been thoroughly explored. The databases of PubMed, Scopus, and Web of Science were searched for pertinent articles in accordance with PRISMA-ScR guidelines. A total of 31 pertinent articles from in vitro and in vivo studies on the anti-inflammatory potentials of iridoids from Rubiaceae were identified. According to current research, genipin, geniposide, and monotropein are the most researched iridoids from Rubiaceae that reduce inflammation. These iridoids primarily act by attenuating inflammatory cytokines and mediators via inhibition of the NF-κB signalling pathway in various disease models. A comprehensive overview of the current research on the anti-inflammatory properties of iridoids from the Rubiaceae family is presented in this review, highlighting the characteristics of the experimental models used as well as the mechanisms of action of these iridoids. To develop an alternative therapeutic agent from iridoids, more studies are needed to elucidate the effects and mechanism of action of iridoids in a wide variety of experimental models as well as in clinical studies pertaining to inflammation-related diseases.

Cornelian Cherry (Cornus mas L.) Fruit Extract Lowers SREBP-1c and C/EBPα in Liver and Alters Various PPAR-α, PPAR-γ, LXR-α Target Genes in Cholesterol-Rich Diet Rabbit Model.

Cornelian cherry (Cornus mas L.) fruits, abundant in iridoids and anthocyanins, are natural products with proven beneficial impacts on the functions of the cardiovascular system and the liver. This study aims to assess and compare whether and to what extent two different doses of resin-purified cornelian cherry extract (10 mg/kg b.w. or 50 mg/kg b.w.) applied in a cholesterol-rich diet rabbit model affect the levels of sterol regulatory element-binding protein 1c (SREBP-1c) and CCAAT/enhancer binding protein α (C/EBPα), and various liver X receptor-α (LXR-α), peroxisome proliferator-activated receptor-α (PPAR-α), and peroxisome proliferator-activated receptor-γ (PPAR-γ) target genes. Moreover, the aim is to evaluate the resistive index (RI) of common carotid arteries (CCAs) and aortas, and histopathological changes in CCAs. For this purpose, the levels of SREBP-1c, C/EBPα, ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), fatty acid synthase (FAS), endothelial lipase (LIPG), carnitine palmitoyltransferase 1A (CPT1A), and adiponectin receptor 2 (AdipoR2) in liver tissue were measured. Also, the levels of lipoprotein lipase (LPL), visceral adipose tissue-derived serine protease inhibitor (Vaspin), and retinol-binding protein 4 (RBP4) in visceral adipose tissue were measured. The RI of CCAs and aortas, and histopathological changes in CCAs, were indicated. The oral administration of the cornelian cherry extract decreased the SREBP-1c and C/EBPα in both doses. The dose of 10 mg/kg b.w. increased ABCA1 and decreased FAS, CPT1A, and RBP4, and the dose of 50 mg/kg b.w. enhanced ABCG1 and AdipoR2. Mitigations in atheromatous changes in rabbits' CCAs were also observed. The obtained outcomes were compared to the results of our previous works. The beneficial results confirm that cornelian cherry fruit extract may constitute a potentially effective product in the prevention and treatment of obesity-related disorders.

Seventeen undescribed iridoid derivatives with anti-inflammatory effects from Hedyotis diffusa and their structure-activity relationships.

Seventeen undescribed iridoid derivatives (1-17) and four known compounds (18-21) were isolated from the whole plant of Hedyotis diffusa Willd. Their structures were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, CD, and 1D and 2D NMR). It is noteworthy that compounds 1-8, which possess unique long-chain aliphatic acid moiety, were reported for the first time among the iridoid natural products. All compounds were evaluated for their anti-inflammatory activities in lipopolysaccharide-induced RAW 264.7 cells. Compounds 2, 4, and 6 showed significant suppression effects on nitric oxide production, with IC50 values of 5.69, 6.16, and 6.84 µM, respectively. The structure-activity relationships of these compounds indicated that long-chain aliphatic moieties at C-10 might be the key group for their anti-inflammatory activities. The therapeutic properties of these iridoid derivatives could give an insight into utilizing H. diffusa as a natural source of anti-inflammatory agents.

Analysis of Differences in the Chemical Composition of Glycosides and Sugars between Four Forms of Fresh Rehmanniae Radix.

Fresh Rehmanniae Radix, as well as its processed products, are widely used in the clinical practice of traditional Chinese medicine. It is mainly available in four forms: fresh Rehmanniae Radix, raw Rehmanniae Radix, prepared Rehmanniae Radix, and nine-steamed, nine-dried Rehmanniae Radix. Pharmacological studies have shown that all Rehmanniae Radix forms contain iridoid glycosides and sugar compounds with various effects, including hypoglycemic, anti-inflammatory, neuroprotective, immunological enhancement, and bone marrow hematopoiesis-promoting activities. Differences in the efficacy among these Rehmanniae Radix forms and their processed products have been attributed to variations in their chemical compositions, particularly in iridoid glycosides and sugar compounds; however, the specific compositional differences in glycosides and sugars among the four forms of Rehmanniae Radix have not been clarified. Therefore, this study aims to qualitatively characterize the iridoid glycosides and sugar compounds in fresh Rehmanniae Radix, raw Rehmanniae Radix, prepared Rehmanniae Radix, and nine-steamed, nine-dried Rehmanniae Radix.

Three Undescribed Iridoid Derivatives Isolated from the Fruits of Vitex trifolia with Their Cytotoxic and Antimicrobial Activities.

Vitex trifolia L. is a medicinal plant and widely distributed in the northern mountainous areas of Vietnam. Phytochemical study on the fruits of this plant led to the isolation of nine iridoid derivatives (1-9) including three undescribed compounds (1-3). Their structures were elucidated to be 3''-hydroxyscrophuloside A1 (1), 3''-hydroxycallicoside D (2), 2'-p-hydroxybenzoylaucubin (3), 6'-p-hydroxybenzoylmussaenosidic acid (4), nishindaside (5), agnuside (6), 10-O-vanilloylaucubin (7), 6'-O-p-hydroxybenzoyl-gardoside (8), and buddlejoside B (9) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1, 2, 4, and 8 significantly posessed anti-barterial activity against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa strains with MIC values in range of 16-64 µg/mL. At concentration of 20 µM, compounds 1-9 did not show cytotoxic effects against human lung cancer cells (PC9).

Preparative separation of iridoid glucosides and crocins from Gardeniae Fructus using sequential macroporous resin column chromatography and evaluation of their anti-inflammatory and antioxidant activities.

Iridoid glycosides (geniposide (GP), genipin-1-gentiobioside (GB), etc.) and crocins (crocin Ⅰ (CR1), crocin Ⅱ(CR2), etc.) are two main bioactive components in Gardeniae Fructus (GF), which is a famous traditional Chinese medicine. Iridoid glycosides exhibit many activities and are used to manufacture gardenia blue pigment for the food industry. Crocins are rare natural water-soluble carotenoids that are often used as food colorants. A sequential macroporous resin column chromatography technology composed of HC-500B and HC-900B resins was developed to selectively separate iridoid glucosides and crocins from GF. The adsorption of GP on HC-900B resin was an exothermic process. The adsorption of CR1 on HC-500B resin was an endothermic process. The two kinds of components were completely separated by a sequential resin column. GB and GP were mainly found in product 1 (P1) with purities of 11.38% and 46.83%, respectively, while CR1 and CR2 were mainly found in product 2 (P2) with purities of 12.32% and 1.40%, respectively. The recovery yields of all the compounds were more than 80%. The above results showed that sequential resin column chromatography technology achieved high selectivity and recovery yields. GF extract, P1 and P2 could significantly inhibit the secretion of nitric oxide (NO), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced RAW264.7 cells, indicating that iridoid glycosides and crocins provide a greater contribution to the anti-inflammatory activity of GF. At the same time, compared to the GF extract and P1, P2 exhibited stronger scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, indicating that crocins may provide a significant contribution to the antioxidant activity of GF.

Iridoids and derivatives from Catalpa ovata with their antioxidant activities.

Six new iridoid derivatives (1-6)，together with twelve known compounds (7-18), were isolated and identified from the dried fruits of Catalpa ovata G. Don. Their chemical structures were mainly established through the relative spectroscopic data, while the absolute configurations of compounds 2 and 3 were elucidated on the electronic circular dichroism calculations. Their antioxidant activities were evaluated by activating the Nrf2 transcriptional pathway in 293 T cells in vitro. Among them, Compounds 1, 3, 4, 6-8, 10-12, 14, 15, 17 and 18 showed significant Nrf2 agonistic effect compared with the control group at 25 µM. Finally, The hypothetical biosynthetic pathway for 1-13 was discussed.

Iridoid-glycoside isolation and purification from Premna fulva leaves.

Premna fulva Craib, rich in iridoid glycosides, is widely used to treat periarthritis, osteoproliferation, pain, and other diseases. However, no studies have reported effective purification methods for obtaining iridoid glycosides as active materials. This paper describes an efficient strategy for separating iridoid glycosides from Premna fulva leaves using high-speed counter-current chromatography and preparative high-performance liquid chromatography. A two-phase solvent system, ethyl acetate/n-butanol/water (7.5:2.5:10, v/v), was selected for high-speed counter-current chromatography separation. The proposed method effectively separated and purified four iridoid glycosides and four lignans, including three new iridoid glycosides (4-6) and five known compounds (1-3, 7, 8), from Premna fulva leaves, indicating that high-speed counter-current chromatography combined with prep-HPLC can efficiently isolate catalpol derivatives from the genus Premna. Additionally, the in vitro anti-inflammatory activities of all isolated compounds were analyzed using lipopolysaccharide-stimulated RAW 264.7 cells, and the results indicated that six compounds (1 and 3-7) exhibited potential anti-inflammatory activities.

[Effects of different drying methods on quality of male flowers of Eucommia ulmoides based on color and chemical composition].

To study the effects of different drying methods on the quality of male flowers of Eucommia ulmoides(MFOEU), we treated fresh MFOEU samples with drying in the shade(DS), vacuum freeze drying(VFD), high-or low-temperature hot air drying(HTHAD, LTHAD), microwave drying(MD), and vacuum drying(VD), respectively. The color, total flavonoid content, total polysaccharide content, and main active components such as geniposide, geniposidic acid, rutin, chlorogenic acid, galuteolin, pinoresinol diglucoside, and aucubin in MFOEU were taken as the evaluation indicators. The quality of MFOEU was comprehensively evaluated by entropy weight method combined with color index method, partial least squares discriminant analysis and content clustering heat map. The experimental results showed that VFD and DS basically kept the original color of MFOEU. The MFOEU treated with MD had higher content of total polysaccharides, phenylpropanoids, lignans, and iridoids. The MFOEU treated with LTHAD had higher content of total flavonoids and that treated with VD had lower content of active components. According to the results of comprehensive evaluation, the quality of MFOEU dried with different methods followed the order of MD>HTHAD>VFD>LTHAD>DS>VD. Considering the color of MFOEU, the suitable drying methods were DS and VFD. Considering the color, active components, and economic benefits of MFOEU, MD was the suitable drying method. The results of this study are of a reference value for the determination of suitable methods for MFOEU processing in the producing areas.

Hepatoprotective Principles from the Rhizomes of Picrorhiza kurroa.

A methanol extract of rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) showed hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. We had previously isolated 46 compounds, including several types of iridoid glycosides, phenylethanoid glycosides, and aromatics, etc., from the extract. Among them, picroside II, androsin, and 4-hydroxy-3-methoxyacetophenone exhibited active hepatoprotective effects at doses of 50-100 mg/kg, per os (p.o.) To characterize the mechanisms of action of these isolates and to clarify the structural requirements of phenylethanoid glycosides for their hepatoprotective effects, their effects were assessed in in vitro studies on (i) D-GalN-induced cytotoxicity in mouse primary hepatocytes, (ii) LPS-induced nitric oxide (NO) production in mouse peritoneal macrophages, and (iii) tumor necrosis factor-α (TNF-α)-induced cytotoxicity in L929 cells. These isolates decreased the cytotoxicity caused by D-GalN without inhibiting LPS-induced macrophage activation and also reduced the sensitivity of hepatocytes to TNF-α. In addition, the structural requirements of phenylethanoids for the protective effects of D-GalN-induced cytotoxicity in mouse primary hepatocytes were evaluated.

Acylated iridoid glucoside and xanthones from Canscora lucidissima: Their structures and ferroptosis inhibitory activity.

Phytochemical study on the whole plants of a Gentianaceous medicinal plant, Canscora lucidissima, gave one new acylated iridoid glucoside, canscorin A (1), and two new xanthone glycosides (2 and 3) together with 17 known compounds including five xanthones, eight xanthone glycosides, two benzophenone glucosides, caffeic acid, and loganic acid. Canscorin A (1) was assigned as a loganic acid derivative having a hydroxyterephthalic acid moiety by spectroscopic analysis together with chemical evidence, while 2 and 3 were elucidated to be a rutinosylxanthone and a glucosylxanthone, respectively. The absolute configurations of the sugar moieties of 2 and 3 were determined by HPLC analysis. The isolated compounds were evaluated for their inhibitory activities against erastin-induced ferroptosis on human hepatoma Hep3B cells and LPS-stimulated IL-1ß production from murine microglial cells.

Anti-inflammatory iridoid glycosides from Paederia scandens (Lour.) Merrill.

Eight previously undescribed iridoid glycosides together with 20 known congeners were isolated from the aerial parts of Paederia scandens (Lour.) Merrill (Rubiaceae). Their structures incorporating absolute configurations were elucidated based on the comprehensive analyses of NMR data, HR-ESI-MS spectrometry, and ECD data. The potential anti-inflammatory activities of the isolated iridoids were evaluated in lipopolysaccharide-stimulated RAW 264.7 macrophages. Compound 6 significantly inhibited the production of nitric oxide with an IC50 value of 15.30 µM. The results of immunoblotting, qPCR, and immunofluorescence staining assays revealed that compound 6 exhibited anti-inflammatory activity by suppressing nuclear translocation of NF-κB and reducing the expression of COX-2, iNOS, IL-1ß, and IL-6. These results provide a basis for further development and utilization of P. scandens as a natural source of potential anti-inflammatory agents.

Isolation, characterization and anticancer activity of secondary metabolites from Verbascum speciosum.

Herein, two iridoid glucosides aucubin (1) and ajugol (2), and two phenyl ethanoids, verbascoside (3) and poliumoside (4) were isolated from the methanol extract of the aerial parts of Verbascum speciosum and used to study about their anticancer activity for the first time. The structures of all compounds were elucidated using spectroscopic data (IR, 1D and 2D NMR, LC-TOF/MS). Antiproliferative activities of Aucubun (1) and Verbascoside (3) were tested against A-549 (human colon cancer), MDA-MD-453 (human breast cancer) and 3T3-L1 (mouse fibroblast)cell lines by XTT assay. In addition, the anticarcer mechanism of action of aucubin (1) was investigated on MDA-MB-453 cells for the first time. XTT result showed that both applied compounds exhibited antiproliferative effect at different dose ranges depending on the cancer type, as well as selectivity between cancer and healty cell lines. Flow cytometry analyzes revealed that aucubin (1) exerts its cytotoxic effect in MDA-MB-453 cells by directing cells to early apoptosis and inhibiting the P13K/AKT signaling pathway.

The total iridoid glycoside extract of Lamiophlomis rotata Kudo induces M2 macrophage polarization to accelerate wound healing by RAS/ p38 MAPK/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Lamiophlomis rotata (Benth.) Kudo (L. rotata), a Tibetan medicinal plant, is used to treat "yellow-water diseases", such as skin disease, jaundice and rheumatism. Our previous study showed that the iridoid glycoside extract of L. rotata (IGLR) is the major constituent of skin wound healing. However, the role of IGLR in the biological process of trauma repair and the probable mechanism of the action remain largely unknown. AIM OF THE STUDY: To investigate the role of IGLR in the biological process of trauma repair and the probable mechanism of the action. MATERIALS AND METHODS: The role of IGLR in wound healing was investigated by overall skin wound in mice with Hematoxylin and Eosin (H&E) and Masson trichrome staining. The anti-inflammatory, angiogenesis-promoting and fibril formation effects of IGLR were visualized in wound skin tissue by immunofluorescence staining, and the proinflammatory factors and growth factors were assayed by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Macrophages, dermal fibroblasts, and endothelial cells were cultured to measure the direct/indirect interaction effects of IGLR on the proliferation and migration of cells, and flow cytometry was employed to assess the role of IGLR on macrophage phenotype. Network pharmacology combined with Western blot experiments were conducted to explore possible mechanisms of the actions. RESULTS: IGLR increased the expression of CD206 (M2 markers) through the RAS/p38 MAPK/NF-κB signaling pathway during wound injury in vivo and in vitro. IGLR suppressed the inflammatory cytokines iNOS, IL-1ß and TNF-α in the early stage of wound healing. During the proliferation step of wound repair, IGLR promoted angiogenesis and fibril formation by increasing the expression of VEGF, CD31, TGF-ß and α-SMA in wound tissue, and similar results were verified by RT-PCR and ELISA. In a paracrine mechanism, the extract promoted the proliferation of dermal fibroblasts, and endothelial cells were founded by the conditioned medium (CM). CONCLUSION: IGLR induced M2 macrophage polarization in the early stage of wound healing; in turn, IGLR played a key role in the transition from inflammation to cell proliferation during the biological process of wound healing.

New iridoids from Patrinia scabiosaefolia and their hypoglycemic effects by activating PI3K/Akt signaling pathway.

Growing in regions of Asia and North America, Patrinia scabiosaefolia is a wild vegetable and herb that has demonstrated health-promoting properties. Iridoids are one of the most bioactive phytochemicals in P. scabiosaefolia but the in-depth study is scarce. Herein we reported the separation and characterization of nine iridoids (compounds 1-9) from P. scabiosaefolia, and two compounds (2 and 6) were new. All the structures of the nine iridoids were characterized and confirmed with NMR (1D & 2D), HRMS, IR and UV. Compound 2 is a five-member ring iridoid, reminiscent of a broken C-1 and C-2 bond. Compound 6 has a typical monoene valerian iridoid, but the 5-deoxyglucose moiety at C-11 position is uncommon in this genus. The anti-diabetic evaluation of the isolated compounds revealed that compounds 1, 2, and 9 significantly increased the glucose absorption in 3 T3-L1 cells (P < 0.01). Further mechanism investigations have demonstrated that compound 1 promoted glucose uptake in dexamethasone-treated 3 T3-L1 adipocytes by activating PI3K/Akt signaling pathway. The expression of GLUT4 mRNA and protein was also upregulated. These results provide scientific references for the potential use of P. scabiosaefolia as a functional food to manage hyperglycemia.