Search Results (19)

Background: The yellow-leaf gl1 mutant of Lagerstroemia indica exhibits an altered phenylpropanoid metabolism pathway compared to wild-type (WT). However, details on the metabolites associated with leaf color variation, including color-specific metabolites with bioactive constituents, are not fully understood. Methods: Chemical and metabolomics approaches were used to compare metabolite composition and antioxidant capacity between the gl1 mutant and WT leaves. Results: The mutant exhibited an irregular xylem structure with a significantly lower phenolic polymer lignin content and higher soluble phenolic compounds. Untargeted metabolomics analysis identified phenolic compounds, particularly lignans, as key differential metabolites between gl1 and WT, with a significant increase in the mutant. The neolignan derivative balanophonin-4-O-D-glu was identified as a characteristic metabolite in the gl1 mutant. The soluble phenolic compounds of the gl1 mutant exhibited higher FRAP, ABTS, DPPH, and hydroxyl radical scavenging activity than in WT. Correlation analysis showed a positive relationship between antioxidant capacity and phenolic compounds in L. indica. Conclusions: Metabolites associated with leaf color variation in the L. indica yellow-leaf gl1 mutant demonstrated high antioxidant capacity, particularly in scavenging hydroxyl radicals. Full article

Equisetum arvense L. (Equisetaceae), widely known as ‘horsetail’, is a perennial plant found extensively across Asia. Extracts of E. arvense have been used in traditional medicine, particularly for the treatment of inflammatory disorders. This study aimed to determine the phytochemical compounds in E. arvense ethanolic extract and their anti-inflammatory properties. Subsequently, we isolated and identified nine secondary metabolites, including kaempferol 3,7-di-O-β-D-glucopyranoside (1), icariside B₂ (2), (Z)-3-hexenyl β-D-glucopyranoside (3), luteolin 5-O-β-D-glucopyranoside (4), 4-O-β-D-glucopyranosyl caffeic acid (5), clemastanin B (6), 4-O-caffeoylshikimic acid (7), (7S,8S)-threo-7,9,9′-trihydroxy-3,3′-dimethoxy-8-O-4′-neolignan-4-O-β-D-glucopyranoside (8), and 3-O-caffeoylshikimic acid (9). The chemical structures of the isolated compounds (1–9) were elucidated using HR-ESI-MS data, NMR spectra, and ECD data. Next, the anti-inflammatory effects of the isolates were evaluated in tumor necrosis factor (TNF)α/interferon (IFN)γ-induced HaCaT, a human keratinocyte cell line. Among the isolates, compound 3 showed the highest inhibitory effect on the expression of pro-inflammatory chemokines, followed by compounds 6 and 8. Correspondingly, the preceding isolates inhibited TNFα/IFNγ-induced activation of pro-inflammatory transcription factors, signal transducer and activator of transcription 1, and nuclear factor-κB. Collectively, E. arvense could be employed for the development of prophylactic or therapeutic agents for improving dermatitis. Full article

Magnolia grandiflora L. (Magnoliaceae) is a plant of considerable medicinal significance; its flowers and seeds have been used in various traditional remedies. Radioligand binding assays of n-hexane seeds extract showed displacement of radioligand for cannabinoid (CB1 and CB2) and opioid δ (delta), κ (kappa), and µ (mu) receptors. Bioactivity-guided fractionation afforded 4-O-methylhonokiol (1), magnolol (2), and honokiol (3), which showed higher binding to cannabinoid rather than opioid receptors in radioligand binding assays. Compounds 1–3, together with the dihydro analog of 2 (4), displayed selective affinity towards CB2R (K_i values of 0.29, 1.4, 1.94, and 0.99 μM, respectively), compared to CB1R (K_i 3.85, 17.82, 14.55, and 19.08 μM, respectively). An equal mixture of 2 and 3 (1:1 ratio) showed additive displacement activity towards the tested receptors compared to either 2 or 3 alone, which in turn provides an explanation for the strong displacement activity of the n-hexane extract. Due to the unavailability of an NMR or X-ray crystal structure of bound neolignans with the CB1 and CB2 receptors, a docking study was performed to predict ligand–protein interactions at a molecular level and to delineate structure-activity relationships (SAR) of the neolignan analogs with the CB1 and CB2 receptors. The putative binding modes of neolignans 1–3 and previously reported related analogs (4, 4a, 5, 5a, 6, 6a, and 6b) into the active site of the CB1 and CB2 receptors were assessed for the first time via molecular docking and binding free-energy (∆G) calculations. The docking and ∆G results revealed the importance of a hydroxyl moiety in the molecules that forms strong H-bonding with Ser383 and Ser285 within CB1R and CB2R, respectively. The impact of a shift from a hydroxyl to the methoxy group on experimental binding affinity to CB1R versus CB2R was explained through ∆G data and the orientation of the alkyl chain within the CB1R. This comprehensive SAR, influenced by the computational study and the observed in vitro displacement binding affinities, has indicated the potential of magnolia neolignans for developing new CB agonists for potential use as analgesics, anti-inflammatory agents, or anxiolytics. Full article

Three pairs of novel enantiomeric 8-O-4′ type neolignans (1a/1b–3a/3b), together with seven known analogues (4–10), were isolated from the whole plants of Saussurea medusa. Their structures were elucidated by extensive spectroscopic data analysis and electric circular dichroism (ECD) calculations after chiral separations. All compounds were obtained from S. medusa for the first time, and compounds 1–3 and 5–10 had never been obtained from the genus Saussurea previously. The anti-inflammatory activities of the compounds were evaluated by determining their inhibitory activities on the production of NO and inducible nitric oxide synthase (iNOS) expression in LPS-stimulated RAW 264.7 cells. Compounds (+)-1a, (−)-1b and 5–7 inhibited NO production and had IC₅₀ values ranging from 14.3 ± 1.6 to 41.4 ± 3.1 μM. Compound 7 induced a dose-dependent reduction in the expression of iNOS in LPS-treated RAW 264.7 cells. Molecular docking experiments showed that all active compounds exhibited excellent docking scores (<−7.0 kcal/mol) with iNOS. Therefore, compounds (+)-1a, (−)-1b and 5–7 isolated from the whole plants of S. medusa may have therapeutic potential in inflammatory diseases. Full article

In our preliminary study, a hot water extract from the fruits of Morus alba (mulberry) inhibited the secretion of metalloproteinase-1 (MMP-1) against tumor necrosis factor-α (TNF-α)-stimulated human dermal fibroblasts (HDFs), and therefore we researched its active compounds. In the present study, a new phenolic glycoside (oddioside A, 1) and 21 known compounds (2−22) were isolated from the hot water extract from the fruits of M. alba by repeated chromatography. The chemical structure of the new compound 1 was elucidated by its spectroscopic data (1D− and 2D−NMR and HRMS) measurement and by acidic hydrolysis. The presence of sargentodoside E (2), eugenyl glucoside (6), 2-O-β-d-glucopyranosyl-4,6-dihydroxybenzaldehyde (7), 7S,8R-erythro-7,9,9’-trihydroxy-3,3’-dimethoxy-8-O-4’-neolignan-4-O-β-d-glucopyranoside (11), pinoresinol-4-O-β-d-glucopyranoside (12), taxifolin-7-O-β-d-glucopyranoside (20), and pinellic acid (21) were reported from M. alba for the first time in this study. The new compound oddioside A (1) suppressed the secretion of MMP-1 and increased collagen in TNF-α-stimulated HDFs. In addition, the phosphorylation of mitogen-activated protein kinases (MAPKs) was inhibited by oddioside A. In conclusion, the extract from fruits of M. alba and its constituent oddioside A may be a potential agent to prevent inflammation-related skin aging and other skin disorders. Full article

Two undescribed compounds, 3β,7β-dihydroxy-24-methylenelanosta-8-ene-11-one (1) and neolignane deightonin (4) were isolated from the aerial parts of Euphorbia deightonii Croizat together with six known compounds, namely, kansenone (2), euphorbol-7-one (3), dehydrodiconiferyl diacetate (5), marylaurencinol D (6), scoparon (7), and 3,4,3′-tri-O-methylellagic acid (8). The structures of the isolated compounds were determined by HRESIMS, 1D (¹H, ¹³C JMOD) and 2D NMR (HSQC, HMBC, ¹H–¹H COSY, NOESY) spectroscopic analysis, and by comparison of the assignments with literature data. The anti-herpes simplex virus type-2 activity of the isolated compounds were investigated by qRT-PCR assay on Vero cells after determining cytotoxic concentration 50% (CC₅₀). Compounds 1, 3, 4, and 7 exhibited inhibitory effects with respective IC₅₀ values of 7.05, 2.42, 11.73, and 0.032 µM. Scoparon (7) showed the strongest anti-HSV activity with a selectivity index of 10.93. Full article

Neolignans honokiol and 4′-O-methylhonokiol (MH) and their derivatives have pronounced anti-inflammatory activity, as evidenced by numerous pharmacological studies. Literature data suggested that cyclooxygenase type 2 (COX-2) may be a target for these compounds in vitro and in vivo. Recent studies of [¹¹C]MPbP (4′-[¹¹C]methoxy-5-propyl-1,1′-biphenyl-2-ol) biodistribution in LPS (lipopolysaccharide)-treated rats have confirmed the high potential of MH derivatives for imaging neuroinflammation. Here, we report the synthesis of four structural analogs of honokiol, of which 4′-(2-fluoroethoxy)-2-hydroxy-5-propyl-1, 1′-biphenyl (F-IV) was selected for labeling with fluorine-18 (T_1/2 = 109.8 min) due to its high anti-inflammatory activity confirmed by enzyme immunoassays (EIA) and neuromorphological studies. The high inhibitory potency of F-IV to COX-2 and its moderate lipophilicity and chemical stability are favorable factors for the preliminary evaluation of the radioligand [¹⁸F]F-IV in a rodent model of neuroinflammation. [¹⁸F]F-IV was prepared with good radiochemical yield and high molar activity and radiochemical purity by ¹⁸F-fluoroethylation of the precursor with Boc-protecting group (15) with [¹⁸F]2-fluoro-1-bromoethane ([¹⁸F]FEB). Ex vivo biodistribution studies revealed a small to moderate increase in radioligand uptake in the brain and peripheral organs of LPS-induced rats compared to control animals. Pretreatment with celecoxib resulted in significant blocking of radioactivity uptake in the brain (pons and medulla), heart, lungs, and kidneys, indicating that [¹⁸F]F-IV is likely to specifically bind to COX-2 in a rat model of neuroinflammation. However, in comparison with [¹¹C]MPbP, the new radioligand showed decreased brain uptake in LPS rats and high retention in the blood pool, which apparently could be explained by its high plasma protein binding. We believe that the structure of [¹⁸F]F-IV can be optimized by replacing the substituents in the biphenyl core to eliminate these disadvantages and develop new radioligands for imaging activated microglia. Full article

In recent years, the use of Sideritis species as bioactive agents is increasing exponentially. The present study aimed to investigate the chemical constituents, as well as the anti-ageing potential of the cultivated Sideritis euboea Heldr. The chemical fingerprinting of the ethyl acetate residue of this plant was studied using 1D and 2D-NMR spectra. Isomeric compounds belonging to acylated flavone derivatives and phenylethanoid glycosides were detected in the early stage of the experimental process through 2D-NMR techniques. Overall, thirty-three known compounds were isolated and identified. Some of them are reported for the first time not only in S. euboea, but also in genus Sideritis L. The anti-ageing effect of the ethyl acetate residue and the isolated specialized products was assessed as anti-hyaluronidase activity. In silico docking simulation revealed the interactions of the isolated compounds with hyaluronidase. Furthermore, the in vitro study on the inhibition of hyaluronidase unveiled the potent inhibitory properties of ethyl acetate residue and apigenin 7-O-β-d-glucopyranoside. Though, the isomers of apigenin 7-O-p-coumaroyl-glucosides and also the 4′-methyl-hypolaetin 7-O-[6′′′-O-acetyl-β-d-allopyranosyl]-(1→2)-β-d-glucopyranoside exerted moderate hyaluronidase inhibition. This research represents the first study to report on the anti-hyaluronidase activity of Sideritis species, confirming its anti-inflammatory, cytotoxic and anti-ageing effects and its importance as an agent for cosmetic formulations as also anticancer potential. Full article

Lindera obtusiloba (LO) BLUME from the genus Lindera (Lauraceae) is a medicinal herb traditionally used in Southeast Asian countries. Indigenously, extracts of different parts of the plant have been used to improve blood circulation and treat allergy, inflammation, rheumatism, and liver diseases. LO is a rich source of therapeutically beneficial antioxidative phytochemicals, such as flavonoids, butenolides, lignans and neolignans. Moreover, recent studies have unravelled the pharmacological properties of several newly found active constituents of LO, such as anti-inflammatory antioxidants (+)-syringaresinol, linderin A, anti-atherosclerotic antioxidant (+)-episesamin, anti-melanogenic antioxidants quercitrin and afzelin, cytotoxic 2-(1-methoxy-11-dodecenyl)-penta-2,4-dien-4-olide, (2Z,3S,4S)-2-(11-dodecenylidene)-3-hydroxy-4-methyl butanolide, anti-allergic koaburaside, (6-hydroxyphenyl)-1-O-beta-d-glucopyranoside and 2,6-dimethoxy-4-hydroxyphenyl-1-O-beta-d-glucopyranoside and the antiplatelet-activity compound Secolincomolide A. These findings demonstrate that LO can be a potential source of antioxidants and other prospective therapeutically active constituents that can lead to the development of oxidative stress-mediated diseases, such as cardiovascular disorders, neurodegenerative disorders, allergies, inflammation, hepatotoxicity, and cancer. Here, the antioxidant properties of different species of Lindera genus are discussed briefly. The traditional use, phytochemistry, antioxidative and pharmacological properties of LO are also considered to help researchers screen potential lead compounds and design and develop future therapeutic agents to treat oxidative stress-mediated disorders. Full article

Acne is a common skin condition observed in adolescents. Nutmeg (Myristica fragrans Houtt) (MF) is a well-known traditional Chinese medicine; its major toxic components, safrole and myristicin, are rich in essential oils. Essential oils of MF (MFO) were extracted by hydrodistillation; the residue was extracted using 50% methanol (MFE-M). The minimum inhibitory concentration (MIC) of MFE-M against Cutibacterium acnes and Staphylococcus aureus was 0.64 mg. Four compounds were obtained from MFE-M: myristicin (1), (+)-erythro-Δ^8′-7S,8R- dihydroxy-3,3,5′-trimethoxy-8-O-4′-neolignan (2), (+)-erythro-Δ^8’-7-hydroxy-3,4,3’,5’-tetramethoxy 8-O-4-neolignan (3), and erythro-Δ^8′-7-acetoxy-3,4,3′,5′-tetramethoxy-8-O-4′-neolignan (4). Compound 2 exerted the strongest antimicrobial activity, with MICs of 6.25 and 3.12 μg/mL against C. acnes and S. aureus, respectively. Moreover, 2 inhibited NO, PGE₂, iNOS, and COX-2 levels in RAW 264.7 cells induced by LPS or heat-killed C. acnes; NO production at 50% inhibitory concentrations (IC₅₀) was 11.07 and 11.53 μg/mL, respectively. Myristicin and safrole content was higher in MFO than in MFE-M. MFO and MFE-M caused no skin irritation after a single topical application in Wistar rats. MFE-M, with low safrole and myristicin content, did not cause skin irritation and exhibited an anti-acne effect; moreover, 2 was identified as the active substance. Therefore, MFE-M could be employed to develop anti-acne compounds for use in cosmetics. Full article

Campanula takesimana Nakai (Campanulaceae; Korean bellflower) is one of the endemic herbs of Korea. The plant has been used as traditional medicines for treating asthma, tonsillitis, and sore throat in Korea. A hot water extract of the leaves of C. takesimana exhibited a significant inhibitory effect on lipopolysaccharide (LPS)-stimulated prostaglandin E₂ (PGE₂) production. Repetitive chromatographic separation of the hot water extract led to the isolation of three new neolignan glucosides, campanulalignans A–C (1–3), with 15 known compounds (4–18). The structures of new compounds 1–3 were elucidated by analyzing nuclear magnetic resonance (NMR) spectroscopic data, along with high resolution quadrupole time of flight mass (HR-Q-TOF-MS) spectrometric data. Among the isolates, simplidin (7), 5-hydroxyconiferaldehyde (11), icariside F₂ (12), benzyl-α-l-arabinopyranosyl-(1″→6′)-β-d-glucopyranoside (13), and kaempferol 3-O-β-d-apiosyl (1→2)-β-d-glucopyranoside (15) were isolated from the Campanulaceae family for the first time. The isolates (1, 2, and 4–18) were assessed for their anti-inflammatory effects on LPS-stimulated PGE₂ production on RAW 264.7 cells. 7R,8S-Dihydrodehydrodiconiferyl alcohol (5), 3′,4-O-dimethylcedrusin 9-O-β-glucopyranoside (6), pinoresinol di-O-β-d-glucoside (8), ferulic acid (10), 5-hydroxyconiferaldehyde (11), and quercetin (18) showed significant inhibitory effects on LPS-stimulated PGE₂ production. Full article

Saururus chinensis (Lour.) Baill. is a perennial herb and grows in Korea, China, and Japan. Interestingly, (7S,8S)-Δ^8′-3,4-methylenedioxy-3′,5,5′-trimethoxy-7-monoacetate-8.O.4′-neolignan (MTMN), one of the active neolignans, was first isolated from the roots of Saururus chinensis. The compound was screened for anti-inflammatory activity using a RAW264.7 murine macrophage cell line. The dried roots of S. chinensis (9.7 kg) were extracted with 70% methanol and then solvent fractionation. From the ethyl acetate fraction, MTMN was purified through silica gel column and reverse-phase column chromatography and its structure was identified by spectroscopic analysis with nuclear magnetic resonance, circular dichroism, and mass spectrometry. RAW264.7 cells were induced using lipopolysaccharide (LPS) and treated with or without MTMN. Production of nitric oxide (NO) and prostaglandin E₂ (PGE₂) levels were measured and protein expressions of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were analyzed by immunoblotting. The isolated neolignan was (7S,8S)-Δ^8′-3,4-methylenedioxy-3′,5,5′-trimethoxy-7-monoacetate-8.O.4′-neolignan. This compound suppressed the LPS-induced iNOS and COX-2 protein expressions, which led to a decrease in the production of NO and PGE₂ levels. Further studies, including in animal models, will be required to establish the precise pharmacological effect of MTMN. Full article

Anti-inflammatory compounds were investigated from the ethanol extract of the roots and rhizomes of Asarum heterotropoides var. mandshuricum, a traditional Chinese medicine called Xixin and used for pain and inflammatory. Nine new compounds were isolated, including six new lignans, neoasarinin A–C (1–3), neoasarininoside A and B (4 and 5), and asarinin B (7), and one new monoterpene, asarincin A (8), two new amides, asaramid II and III (10 and 11), and one new natural monoterpene, asaricin B (9), along with 37 known compounds (6, 12–47). Their structures and absolute configurations were elucidated on the basis of spectroscopic methods and chemical analyses. This is the first report of the absolute configuration of asarinin A (6). The 8-O-4′ neolignans (1–5) were reported in the genus Asarum for the first time. The 15 compounds 17, 19, 22–25, 28, 31, 36, 40, 42, 43, 45–47 were isolated from the genus Asarum, and compounds 16, 32, 33, 37 and 39 were isolated from A. heterotropoides var. mandshuricum for the first time. Thirty-seven of the isolates were evaluated for anti-inflammatory activity against the release of β-glucuronidase in polymorphonuclear leukocytes (PMNs) induced by the platelet-activating factor (PAF), and compounds 1, 4, 7, 8, 14, 17–19, 22, 24, 25, 29, 30, 32, 33, 40–43, 45, and 46 showed potent anti-inflammatory activities in vitro, with 27.9%–72.6% inhibitions at 10⁻⁵ mol/L. The results of anti-inflammatory assay suggested that lignans obtained from the CHCl₃ extract might be the main active components of Xixin. Full article

Aschantin is a bioactive neolignan found in Magnolia flos with antiplasmodial, Ca²⁺-antagonistic, platelet activating factor-antagonistic, and chemopreventive activities. We investigated its inhibitory effects on the activities of eight major human cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferase (UGT) enzymes of human liver microsomes to determine if mechanistic aschantin–enzyme interactions were evident. Aschantin potently inhibited CYP2C8-mediated amodiaquine N-de-ethylation, CYP2C9-mediated diclofenac 4′-hydroxylation, CYP2C19-mediated [S]-mephenytoin 4′-hydroxylation, and CYP3A4-mediated midazolam 1′-hydroxylation, with K_i values of 10.2, 3.7, 5.8, and 12.6 µM, respectively. Aschantin at 100 µM negligibly inhibited CYP1A2-mediated phenacetin O-de-ethylation, CYP2A6-mediated coumarin 7-hydroxylation, CYP2B6-mediated bupropion hydroxylation, and CYP2D6-mediated bufuralol 1′-hydroxylation. At 200 µM, it weakly inhibited UGT1A1-catalyzed SN-38 glucuronidation, UGT1A6-catalyzed N-acetylserotonin glucuronidation, and UGT1A9-catalyzed mycophenolic acid glucuronidation, with IC₅₀ values of 131.7, 144.1, and 71.0 µM, respectively, but did not show inhibition against UGT1A3, UGT1A4, or UGT2B7 up to 200 µM. These in vitro results indicate that aschantin should be examined in terms of potential interactions with pharmacokinetic drugs in vivo. It exhibited potent mechanism-based inhibition of CYP2C8, CYP2C9, CYP2C19, and CYP3A4. Full article

The blood-brain barrier (BBB) permeability of twelve lignans and three phenolic malabaricones from the seeds of Myristica fragrans (nutmeg) were studied with the MDCK-pHaMDR cell monolayer model. The samples were measured by high-performance liquid chromatography and the apparent permeability coefficients (P_app) were calculated. Among the fifteen test compounds, benzonfuran-type, dibenzylbutane-type and arylnaphthalene-type lignans showed poor to moderate permeabilities with P_app values at 10⁻⁸–10⁻⁶ cm/s; those of 8-O-4′-neolignan and tetrahydrofuran-lignan were at 10⁻⁶–10⁻⁵ cm/s, meaning that their permeabilities are moderate to high; the permeabilities of malabaricones were poor as their P_app values were at 10⁻⁸–10⁻⁷ cm/s. To 5-methoxy-dehydrodiisoeugenol (2), erythro-2-(4-allyl-2,6-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)-propan-1-ol acetate (6), verrucosin (8), and nectandrin B (9), an efflux way was involved and the main transporter for 6, 8 and 9 was demonstrated to be P-glycoprotein. The time and concentration dependency experiments indicated the main transport mechanism for neolignans dehydrodiisoeugenol (1), myrislignan (7) and 8 was passive diffusion. This study summarized the relationship between the BBB permeability and structure parameters of the test compounds, which could be used to preliminarily predict the transport of a compound through BBB. The results provide a significant molecular basis for better understanding the potential central nervous system effects of nutmeg. Full article