As part of an ongoing search for new anti-inflammatory agents from medicinal plants, five new dimeric and trimeric flavonoids (1-5) were isolated from the roots of Pistacia weinmannifolia. The structures of pistachalcone A (1), pistachalcone B (2), pistaflavanone A (3), pistachalcone C (4), and pistachalcone D (5) were elucidated by the analysis of spectroscopic data. The known compounds rhuschalcone II (6), rhuschalcone VI (7), and pauferrol B (8) were also isolated and identified. Our in vitro analysis found that compounds isolated from P. weinmannifolia root extract exert anti-inflammatory effects in phorbol myristate acetate (PMA)-induced NCI-H292 airway epithelial cells by the suppression of expression levels such as interleukin-8 (IL-8) and mucin 5AC (MUC5AC), which are closely related to the pulmonary inflammatory response in the pathogenesis of COPD. Therefore, these dihydrochalcone derivatives may have value as new starting materials for the development of drug candidates against COPD.

Centella asiatica (L.) Urban is an herbaceous perennial plant of the Apiaceae family that has diverse medicinal uses. Its active components are saponin, phenolics, and polyacetylenes. Plant cell cultures have been exploited for the efficient production of metabolites with pharmacological activity. In this work, we prepared adventitious root cultures of C. asiatica and analyzed their content and biological activity. Adventitious root extracts were found to increase glucose uptake by differentiated L6 skeletal muscle cells and to be more efficient than the extract of whole plants. Chromatographic fractionation of the extracts from adventitious roots of C. asiatica led to the isolation of two known polyacetylenes, araliadiol (1) and 8-acetoxy-1,9-pentadecadiene-4,6-diyn-3-ol (2), in addition to a new polyacetylene, which we have named centellidiol (3). All the three polyacetylenes stimulated glucose uptake in a dose-dependent manner. The methanol extract of adventitious roots contained 0.53% and 0.82% of compounds 1 and 2, respectively, which are values that were 15 and 21 times higher that are found in mother plants. We therefore suggest that the high content of these polyacetylenes contributes to the high efficacy of C. asiatica adventitious root cultures. Overall, adventitious root cultures of C. asiatica can be part of a secure supply of effective ingredients including polyacetylenes.

The purpose of this study is to demonstrate the potential enhancement of the flavonoid contents from Agastache rugosa, which can be obtained as raw materials for functional products in the food medicine industry by identifying important factors for efficient preparation to save costs and time in terms of economic factors.For this reason, response surface methodology using Box-Behnken design was used to optimize the extraction conditions for the maximum yield of seven major compounds from A. rugosa.The optimum conditions were obtained with an ethanol concentration of 60.0%, a temperature of 50 o C, and an extraction time of 33.6 min, meaning that the regression analysis fits the experimental data well.Under these conditions, the seven major compounds 1-7 had observed values of 2.169, 2.135, 0.697, 2.485, 0.105, 1.247, and 0.551%, respectively.These results show that the observed values are in good agreement with the predicted values in the regression model.This process for optimization study exhibited a basic protocol for obtaining stable ingredients from A. rugosa that are appropriate for the development of effective functional products.

Ligustrum lucidum Aiton is a flowering plant of the Oleaceae family, and its fruits have been traditionally used for skin nourishment and the treatment of skin diseases. However, the anti-inflammatory constituents for skin disease are not well-characterized. Phytochemical investigation of L. lucidum fruits resulted in the isolation of a new secoiridoid, secoligulene (1), together with (E)-3-(1-oxobut-2-en-2-yl)pentanedioic acid (2) and trans-(E)-3-(1-oxobut-2-en-2-yl)glutaric acid (3). Secoligulene (1) displayed the potent inhibitory effect on NO production with an IC50 value of 12.0 μg/mL. Secoligulene (1) also downregulated mRNA transcriptional levels of pro-inflammatory cytokines such as IL-1 α, IL-1β, IL-6 and COX-2 in LPS-stimulated RAW264.7 cells. Further investigation showed that secoligulene (1) inhibited the phosphorylation of IκB and JNK activated by LPS. In addition, secoligulene (1) downregulated the expression of chemokines such as CXCL8 and CCL20 in the TNF-α/IL-17/IFN-γ induced HaCaT psoriasis model. Taken together, these findings support the beneficial effects of L. lucidum and its constituents on inflammation-related skin diseases and can be further developed as therapeutic treatments for related diseases.

Age-related macular degeneration (AMD) is a major cause of vision loss in the elderly population. Anti-vascular endothelial growth factor (VEGF) antibody therapy is applicable to neovascularisation of AMD; however, the prevention of fibrosis after anti-VEGF monotherapy is an unmet medical need. Subretinal fibrosis causes vision loss in neovascular age-related macular degeneration (nAMD) even with anti-VEGF therapy. We report the anti-fibrotic and anti-neovascularisation effects of alpinumisoflavone (AIF), an isoflavonoid derived from unripe Maclura tricuspidata fruit, in in vitro and in vivo models. For in vitro study, we treated H 2 O 2 or THP-1 conditioned media (TCM) following activation with phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS) in a human retinal pigment epithelial cell line (ARPE-19). Choroidal neovascularisation (CNV) was induced by laser photocoagulation in mice, immediately followed by intravitreal administration of 25 μg AIF. CNV area and fibrosis were measured 7 days after laser photocoagulation. AIF showed anti-fibrosis and anti-neovascularisation effects in both the models. The laser induced CNV area was reduced upon AIF administration in nAMD mouse model. Additionally, AIF decreased the levels of the cleaved form of crystallin alpha B (CRYAB), a chaperone associated with VEGF stabilisation and fibrosis. Our results demonstrate a novel therapeutic application of AIF against neovascularisation and fibrosis in nAMD.

Investigation of chemical constituents of Masclura tricuspidata leaves resulted in the isolation of 47 isoflavonoids possessing prenyl groups with different numbers and structures. Among them, sixteen compounds named cudracusisoflavones A-P (1-16) were first isolated from nature. The isoflavonoids isolated from M. tricuspidata leaves showed anti-diabetic effects as measured by inhibition on alpha-glucosidase activity and advanced glycation end-products (AGEs) formations. Especially, cudracusisoflavone L (12), a new compound, together with gancaonin M (27), erysenegalensein E (41) and millewanin G (44) showed strong a-glucosidase inhibition with IC50 values <10.0 mu M. In addition, cudracusisoflavones A (1), D (4), M (13) and N (14), together with known prenylated isoflavonoids efficiently inhibited methylglyoxal (MGO)- or glyoxal (GO)-induced AGE formations. Structure activity relationship together with molecular docking analysis suggested the importance of hydroxy group and linear type of prenyl moiety for alpha-glucosidase inhibition. Conclusively, diverse prenylated isoflavonoids in M. tricuspidata leaves might ameliorate glycotoxicity-induced metabolic diseases.

Masclura tricuspidata, also called as Cudrania tricuspidata, is one of the most common Moraceae family plants in East Asia. Its trivial name follows mulberry due to the similar morphology. Investigation of the bioactive constituents of M. tricuspidata leaves yielded a new xanthone derivative along with twenty known compounds through various chromatographic techniques. A new compound was defined as mascluraxanthone (3), a prenylated xanthone glucoside on the basis of 1D and 2D NMR and MS data. Twenty known compounds were identified as four xanthone derivatives (1-2 and 4-5), two flavans (6-7), six flavanol derivatives (8-13), a flavonone (14) and seven flavonol derivatives (15-21). Among the isolated compounds, flavanol and flavonoid derivatives with 3′,4′-OH groups showed antioxidant and anti-tyrosinase activities. Conclusively, the leaves of M. tricuspidata are rich in aromatic compounds including xanthones and flavonoids. In addition, these constituents showed antioxidant and anti-tyrosinase potentials, which might be useful for oxidative stress related diseases.

Maclura tricuspidata, which belongs to the Moraceae family, is widely distributed in Asia, including Korea. All parts of this plant, such as roots, fruits, and leaves, are rich in diverse bioactive compounds, especially xanthones and isoflavonoids. Investigation of the leaves of M. tricuspidata through various chromatographic techniques yielded fourteen compounds, including five new compounds. The new compounds were determined to comprise an isoflavonoid structure with hydroxyethyl moiety and defined as hydroxyethylisoflavones A-E (10-14) on the basis of 1D and 2D NMR and MS data. These compounds efficiently inhibited α-glucosidase activity.

Wild ginseng ( Panax ginseng ) adventitious root cultures were prepared by elicitation using methyl jasmonate and investigated further to find new secondary metabolites. Chromatographic fractionation of wild ginseng adventitious root cultures led to the isolation of eleven compounds. The chemical structures of isolated compounds were identified as four known flavanone derivatives ( 1 – 4 ), one new curcubinoyl derivative, jasmogin A ( 5 ) and six new curcubinoyl-flavanone conjugates, jasmoflagins A-F ( 6 – 11 ) by extensive spectroscopic analysis. Newly isolated curcubinoyl derivatives showed inhibitory activity against lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages. Therefore, our present study suggested that elicitor stimulated plant cell cultures might contribute to the production of new metabolites.

Wild ginseng ( Panax ginseng ) adventitious root cultures were prepared by elicitation using methyl jasmonate and investigated further to find new secondary metabolites. Chromatographic fractionation of wild ginseng adventitious root cultures led to the isolation of eleven compounds. The chemical structures of isolated compounds were identified as four known flavanone derivatives ( 1 – 4 ), one new curcubinoyl derivative, jasmogin A ( 5 ) and six new curcubinoyl-flavanone conjugates, jasmoflagins A-F ( 6 – 11 ) by extensive spectroscopic analysis. Newly isolated curcubinoyl derivatives showed inhibitory activity against lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages. Curcubinoyl moiety is structurally similar with methyl jasmonate, which was used as an elicitor. Therefore, our present study suggested that elicitor might increase the content of active constituents and also contribute to the production of new metabolites by participation as precursors in biosynthesis. Taken together, plant cell cultures are useful not only for efficient production of active compounds but also development of new secondary metabolites.

Four compounds, hericerin (1), isohericerinol A (2), N-de-phenylethyl isohericerin (3) and corallocin A (4) were isolated from the fruiting bodies of Hericium erinaceus, a lion's mane mushroom (Hericiaceae). Among them, isohericerinol A (2) was newly reported in nature. Further investigation of the neurotrophic effect of isolated compounds demonstrated that isohericerinol A (2) strongly increased the nerve growth factor (NGF) production in C6 glioma cells followed by corallocin A (4) and hericerin (1). Increased NGF production by these compounds promoted the neurite outgrowth in N2a neuronal cells. Western blot analysis also showed the increased protein expression of NGF, brain-derived neurotrophic factor (BDNF) and synaptophysin (SYP) in C6-N2a cells. Taken together, our present study characterized the neurotrophic constituents of H. erinaceus, which may support the potential use of memory improvement.

The composition of a plant, together with its efficacy, vary depending on its maturity and plant parts. In this study, the chemical constituents of immature fruits of Maclura tricuspidata (Moraceae) were investigated together with their anti-diabetic and antioxidant effects. A total of 34 compounds were isolated from the immature fruits of M. tricuspidata using various chromatographic methods. Structure elucidation using extensive spectroscopic analysis led to the characterization of isolated compounds as isoflavonoids with prenyl substituents. Among them, macluraisoflavones A-O were first isolated from nature. The anti-diabetic and antioxidant activity of the isolated compounds were also suggested by α-glucosidase inhibitory activity and DPPH radical scavenging activity, respectively. In particular, macluraisoflavone I, an isoflavonoid with 2,2-dimethylpyran and 2-hydroperoxy-3-methylbut-3-enyl moieties, showed potent α-glucosidase inhibitory activity and DPPH radical scavenging activity. Further molecular docking analysis suggested hydrogen bond and alkyl interactions between α-glucosidase and macluraisoflavone I. Therefore, the immature fruits of M. tricuspidata can be used as an important natural product with antioxidant and anti-diabetic properties.

Streptococcus zoonotic bacteria cause serious problems in aquaculture with clinical effects on humans. A structure-antibacterial activity relationships analysis of 22 isoflavones isolated from M. tricuspidata (leaves, ripe fruits, and unripe fruits) against S. iniae revealed that prenylation of the isoflavone skeleton was an important key for their antibacterial activities (minimum inhibitory concentrations: 1.95–500 μg/mL). Through principal component analysis, characteristic prenylated isoflavones such as 6,8-diprenlygenistein (4) were identified as pivotal compounds that largely determine each part’s antibacterial activities. M. tiricuspidata ripe fruits (MTF), which showed the highest antibacterial activity among the parts tested, were optimized for high antibacterial activity and low cytotoxicity on fathead minnow cells using Box–Behnken design. Optimized extraction conditions were deduced to be 50%/80 °C/7.5 h for ethanol concentration/extraction temperature/time, and OE-MTF showed contents of 6,8-diprenlygenistein (4), 2.09% with a MIC of 40 µg/mL. These results suggest that OE-MTF and its active isoflavones have promising potential as eco-friendly antibacterial agents against streptococcosis in aquaculture.

Ethnopharmacological relevance: Hericium erinaceus, commonly called lion's mane mushroom, is an edible and medicinal mushroom that has been traditionally used for the treatment of metabolic disorders, gastrointestinal diseases and memory impairment. In this study, potential anti-hyperglycemic constituents were identified to support the traditional usage of H. erinaceus. Materials and methods: The components of H. erinaceus were purified using various column chromatography techniques. The structure of the separated compounds was determined based on spectroscopic data analysis, i.e., 1D and 2D NMR analysis. The anti-hyperglycemic activity of the isolated compounds was evaluated by measuring the inhibitory effects on alpha-glucosidase activity. Molecular docking analysis was also conducted for elucidation of alpha-glucosidase inhibitory activity of isolated compounds. Results: Ten compounds including four new compounds, erinacenols A-D (1-4), were isolated from the fruiting bodies of H. erinaceus. Investigation of the anti-hyperglycemic effect of isolated compounds demonstrated that erinacenol D (4), 4-[3 ',7 '-dimethyl-2 ',6 '-octadienyl]-2-formyl-3-hydroxy-5-methyoxybenzylalcohol (6), hericene A (7), hericene D (8) and hericenone D (9) strongly inhibited alpha-glucosidase activity with IC50 values of <20 mu M. The structure activity relationship suggested the importance of long side chain for alpha-glucosidase inhibitory activity. Further analysis by molecular docking demonstrated the interaction of alpha-glucosidase and isolated compounds, which supported the inhibitory activity of alpha-glucosidase. Conclusion: Our present study demonstrated the beneficial effect of H. erinaceus by characterization of alpha-glucosidase inhibitory compounds, including four new compounds. This approach can be valuable support for the traditional use of H. erinaceus for the treatment of diabetes and metabolic diseases, which needs to be clarified by further in-vivo study.

Actinidia arguta, commonly called hardy kiwifruit or kiwiberry, has cold-resistant properties and can be cultivated in Asia, including Korea. Seven new triterpenoids (2-4 and 8-11) along with eight known triterpenoids were isolated from the leaves of A. arguta through various chromatographic techniques. The new triterpenoids were defined as actiniargupenes A-C (2-4), actinidic acid derivatives with phenylpropanoid constituent units, dehydroisoactinidic acid (8), and actiniargupenes D-F (9-11), asiatic acid derivatives with phenylpropanoid substituents, on the basis of 1D and 2D NMR and MS data. Among the triterpenoids, those with a phenylpropanoid constituent unit showed inhibitory activity on α-glucosidase, which suggested the importance of the phenylpropanoid moiety. Molecular docking analysis demonstrated the interaction between the 4'-OH group of the phenylpropanoid moiety and α-glucosidase.

Nine new compounds, argutinosides A-I (1-9) together with 20 known compounds (10-29), were isolated from the fruits of Actinidia arguta. Using spectral analysis, the structures of the isolated compounds were identified as 10 succinic acid derivatives, 11 quinic acid derivatives, two shikimic acid derivatives and six citric acid derivatives. The NF-kappa B transcriptional inhibitory activity of the compounds was evaluated using RAW 264.7 macrophages cells induced by lipopolysaccharide. Among four groups of different organic acid derivatives, the quinic acid derivatives inhibited NF-kappa B transcriptional activity with an IC50 value of 4.0 mu M. Fruit is rich in organic acid and secondary metabolites, which differ depending on the type of fruit. Our present study showed the presence of various organic acids conjugates including nine new 2-methylsuccinic acid phenolic conjugates in kiwiberry and compared their biological activities. This will contribute to application of kiwiberry and also the diversity of different fruits.

The leaves of Laurus nobilis, commonly called as bay leaves, have been traditionally used for the treatment of inflammatory symptoms. As a part of the research on the characterization of bioactive constituents from natural products, twenty one sesquiterpene lactones were isolated from the leaves of L. nobilis. Among them, laurenoperoxylides A (1) and B (2) were first reported in nature and sivosinolide (11), altissin (12), maroniolid (13) and 4 alpha-hydroxy-guaia-10(14), 11(13)-diene-12,6 alpha-olide (20) were first isolated from this plant. The anti-inflammatory activity of isolated compounds was evaluated by measuring their effects on the NF-kappa B transcriptional activity induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages cells. Among twenty one sesquiterpenes, 11-exo-methylenesantonin (9) exerted the most potent inhibition with an IC50 value of 4.0 mu M. Santamarine (4), magnolialide (5) and zaluzanin D (18) also significantly inhibited NF-kappa B activity with IC50 values of < 10 mu M. Conclusively, sesquiterpene lactones from L. nobilis inhibited LPS-induced NF-kappa B transcriptional activity in RAW 264.7 cells, which support the use of L. nobilis against inflammation.

Toxicodendron vernicifluum, also called as Rhus verniciflua is a deciduous tree belonging to Anacardiaceae family. Two new caffeoyl threonate esters, rhuseols A (1) and B (2), together with 5-O-(E)-caffeoylquinic acid methyl ester (3) were isolated from the leaves of T. vernicifluum. The structures of isolated compounds were established by using 1D and 2D NMR in combination with HR-ESI-MS. Compounds 1 – 3 showed DPPH radical scavenging effects with IC50 values of 47.9, 107.8 and 15.4 µM, respectively. Taken together, these compounds might contribute to the antioxidant properties of the leaves of T. vernicifluum, which will be useful for various oxidative stress mediated diseases.

Phytochemical investigation of the roots of Taraxacum coreanum (Asteraceae) led to the isolation of two new sesquiterpenes, acetyldihydrotaraxinolide (2) and acetyltaraxinolide (4), together with two known sesquiterpene glycosides, 11β,13-dihydrotaraxinic acid (1) and taraxinic acid β-(6-O-acetyl)-glucopyranosyl ester (3). The structures of the isolated compounds were determined on the basis of spectroscopic analysis.