The crude extract obtained from Cinnamomum macrostemon Hayata regulates oxidative stress and mitophagy in keratinocytes.

Four ethanol fractionated crude extracts (EFCEs [A-D]) purified from the leaves of Cinnamomum macrostemon Hayata were screened for antioxidative effects and mitochondrial function in HaCaT cells. The higher cell viability indicated that EFCE C was mildly toxic. Under the treatment of 50 ng/mL EFCE C, the hydrogen peroxide (H2O2)-induced cytosolic and mitochondrial reactive oxygen species levels were reduced as well as the H2O2-impaired cell viability, mitochondrial membrane potential (MMP), ATP production, and mitochondrial mass. The conversion of globular mitochondria to tubular mitochondria is coincident with EFCE C-restored mitochondrial function. The mitophagy activator rapamycin showed similar effects to EFCE C in recovering the H2O2-impaired cell viability, MMP, ATP production, mitochondrial mass, and also mitophagic proteins such as PINK1, Parkin, LC3 II, and biogenesis protein PGC-1α. We thereby propose the application of EFCE C in the prevention of oxidative stress in skin cells.

Secondary Metabolites with Antifungal Activities from Mangrove Derived Fungus Monascus purpureus WMD2424.

The mold Monascus, also called red yeast rice, anka, or koji, has been used as the natural food coloring agent and food additives for more than 1000 years in Asian countries. It has also been used in Chinese herbology and traditional Chinese medicine due to its easing digestion and antiseptic effects. However, under different culture conditions, the ingredients in Monascus-fermented products may be changed. Therefore, an in-depth understanding of the ingredients, as well as the bioactivities of Monascus-derived natural products, is important. Here, through the thorough investigation into the chemical constituents of M. purpureus wmd2424, five previously undescribed compounds, monascuspurins A-E (1-5), were isolated from the EtOAc extract of mangrove-derived fungus Monascus purpureus wmd2424 cultured in RGY medium. All the constituents were confirmed via HRESIMS and 1D- and 2D-NMR spectroscopy. Their antifungal activity was also evaluated. Our results showed that four constituents (compounds 3-5) possessed mild antifungal activity against Aspergillus niger, Penicillium italicum, Candida albicans, and Saccharomyces cerevisiae. It is worth mentioning that the chemical composition of the type strain Monascus purpureus wmd2424 has never been studied.

Two new chromones and a new coumarin from the fruit of Cnidium monnieri (L.) Cusson.

Two new chromones named cnidimol G (1) and cnidimol H (2), one new coumarin, 7-methoxy-8-(3-methoxy-3-methyl-2-oxobutyl)coumarin (3), and twenty known compounds were isolated from MeOH extract of the fruit of Cnidium monnieri (L.) Cusson. The structures of compounds were elucidated by extensive spectroscopic analyses including 1 D and 2 D NMR, HRESIMS, IR and UV. Anti-inflammatory activity of the selected isolated compounds were evaluated. Compounds 1 and 8 exhibited inhibitory activities against nitric oxide production.

Undescribed alkyne-geranylcyclohexenetriols from the endophyte Diaporthe caulivora 09F0132 and their anti-melanogenic activity.

To explore valuable endophytic fungus from Formosan Lauraceous plants as natural medicinal products, the fungus, Diaporthe caulivora isolated from leaves of Neolitsea daibuensis, was investigated. Through a thorough investigation of the ethanolic extract of the solid fermentation of D. caulivora 09F0132, six undescribed alkyne-geranylcyclohexenetriols, caulivotrioloxins A-F, one undescribed trichopyrone, diapopyrone, two undescribed sesquiterpenes, caulibysins A-B, one compound firstly isolated from the natural source, 3-O-desmethyl phomentrioloxin, and eight known compounds have been successfully identified. The absolute configuration of caulibysin A was confirmed by single-crystal X-ray diffraction, and those of (3R,8S)-5,7-dihydroxy-3-(1-hydroxyethyl)phthalide and (3S,8S)-5,7-dihydroxy-3-(1-hydroxyethyl)phthalide were determined by circular dichroism (CD) spectra. Among the isolated compounds, caulivotrioloxin A concentration-dependently decreased the cellular melanin contents and tyrosinase activities in mouse melanoma B16-F10 cells, suggesting the anti-melanogenic potentials. The anti-melanogenic effects of caulivotrioloxin A involved the decrease in the protein expressions of melanogenic enzymes, including tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. Taken together, these results suggested that the isolates from D. caulivora could be served as natural melanogenesis inhibitors for cosmeceutical applications.

Secondary Metabolites with Anti-Inflammatory from the Roots of Cimicifuga taiwanensis.

The genus Cimicifuga is one of the smallest genera in the family Ranunculaceae. Cimicifugae Rhizoma originated from rhizomes of Cimicifuga simplex, and C. dahurica, C. racemosa, C. foetida, and C. heracleifolia have been used as anti-inflammatory, analgesic and antipyretic remedies in Chinese traditional medicine. Inflammation is related to many diseases. Cimicifuga taiwanensis was often used in folk therapy in Taiwan for inflammation. Phytochemical investigation and chromatographic separation of extracts from the roots of Cimicifuga taiwanensis has led to the isolation of six new compounds: cimicitaiwanins A-F (1-6, respectively). The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic data analysis (1D- and 2D-NMR, MS, and UV) and comparison with the literature data. The effect of some isolates on the inhibition of NO production in lipopolysaccharide-activated RAW 264.7 murine macrophages was evaluated. Of the isolates, 3-6 exhibited potent anti-NO production activity, with IC50 values ranging from 6.54 to 24.58 µM, respectively, compared with that of quercetin, an iNOS inhibitor with an IC50 value of 34.58 µM. This is the first report on metabolite from the endemic Taiwanese plant-C. taiwanensis.

Comparison of Various Solvent Extracts and Major Bioactive Components from Unsalt-Fried and Salt-Fried Rhizomes of Anemarrhena asphodeloides for Antioxidant, Anti-α-Glucosidase, and Anti-Acetylcholinesterase Activities.

The rhizome of Anemarrhena asphodeloides Bunge (AA, family Liliaceae) is a famous and frequently used herbal drug in the traditional medicine of Northeast Asia, under vernacular name "zhimu". A. asphodeloides has been used as an anti-inflammatory, antipyretic, anti-platelet aggregation, anti-depressant, and anti-diabetic agent in traditional Chinese medicine. We examined the antioxidant, anti-acetylcholinesterase (AChE), and anti-α-glucosidase activities of various solvent extracts and the main bioactive compounds from the rhizome of A. asphodeloides. Acetone extract exhibited comparatively high antioxidant activities by 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, and ferric-reducing antioxidant power (FRAP) assays. A water extract exhibited relatively strong antioxidant activity by superoxide radical scavenging test. Furthermore, dichloromethane, chloroform, and n-hexane extracts showed significant anti-α-glucosidase activities. Finally, ethanol and dichloromethane extracts exhibited relatively strong AChE inhibitory activity. HPLC analysis was used to examine and compare various solvent extracts for their compositions of isolates. We isolated four major chemical constituents and analyzed their antioxidant, anti-α-glucosidase, and AChE inhibitory activities. The bioactivity assays showed that mangiferin displayed the most potential antioxidant activities via FRAP, ABTS, DPPH, and superoxide assays and also exhibited the most effective anti-AChE and anti-α-glucosidase activities among all the isolates. The present study suggests that A. asphodeloides and its active extracts and components are worth further investigation and might be expected to develop as a candidate for the treatment or prevention of oxidative stress-related diseases, AChE inhibition, and hyperglycemia.

Secondary Metabolites with Antimicrobial Activities from Chamaecyparis obtusa var. formosana.

Seven new compounds, including one dimer novel skeleton, chamaecyformosanin A (1); three diterpenes, chamaecyformosanins B-D (2-4); one sesquiterpene, chamaecyformosanin E (5); and two monoterpenes, chamaecyformosanins F and G (6 and 7) were isolated from the methanol extract of the bark of Chamaecyparis obtusa var. formosana. Their structures were established by the mean of spectroscopic analysis and the comparison of NMR data with those of known analogues. Their structures were elucidated on the basis of physicochemical evidence, in-depth NMR spectroscopic analysis, and high-resolution mass spectrometry. Furthermore, the isolated compounds were subjected to an evaluation of their antimicrobial activity. Metabolites 1, 3, and 4 present antibacterial activities. It is worth mentioning that the chemical composition of the bark of C. obtusa var. formosana has never been studied in the past. This is the first time the barks from C. obtusa var. formosana were studied and two new skeleton compounds, 1 and 7, were obtained.

Novel Antifungal Dimers from the Roots of Taiwania cryptomerioides.

Five new dimer compounds, namely Taiwaniacryptodimers A-E (1-5), were isolated from the methanol extract of the roots of Taiwania cryptomerioides. Their structures were established by mean of spectroscopic analysis and comparison of NMR data with those of known analogues. Their antifungal activities were also evaluated. Our results indicated that metabolites 1, 2, 4, and 5 displayed moderate antifungal activities against Aspergillus niger, Penicillium italicum, Candida albicans, and Saccharomyces cerevisiae.

Different types of components obtained from Monascus purpureus with neuroprotective and anti-inflammatory potentials.

The mold Monascus has been used as a natural food coloring agent and food additive for more than 1000 years in Asian countries. In Chinese herbology, it was also used for easing digestion and antiseptic effects. Through a thorough investigation of a citrinin-free strain: M. purpureus BCRC 38110, four azaphilones, three benzenoids, one benzofuranone, one 5',6'-dihydrospiro[isochromane-1,2'-pyran]-4'(3'H)-one derivative, two steroids, and six tetralones have been successfully identified. Among them, monapyridine A (1), monatetralones A-E (2-6), and monabenzofuranone (7) were first reported. Their structures were characterized by 1D and 2D NMR, UV, IR, and HRESIMS analyses. With a series of bioactivity screening, monascuspirolide B (14) and ergosterol peroxide (16) exhibited concentration-dependent attenuation of the paclitaxel-induced neurite damage of mouse dorsal root ganglion neurons. The interleukin (IL)-1ß-induced release of inflammatory cytokines IL-8 and tumor necrosis factor (TNF)-α in human chondrosarcoma cells was inhibited by monapurpureusone (8) and monascuspirolide B (14). Altogether, M. purpureus BCRC 38110 possessed potentials as natural therapeutics against inflammatory osteoarthritis and paclitaxel-induced neurotoxicity.

Secoiridoid Glucosides and Anti-Inflammatory Constituents from the Stem Bark of Fraxinus chinensis.

Qin Pi (Fraxinus chinensis Roxb.) is commercially used in healthcare products for the improvement of intestinal function and gouty arthritis in many countries. Three new secoiridoid glucosides, (8E)-4''-O-methylligstroside (1), (8E)-4''-O-methyldemethylligstroside (2), and 3'',4''-di-O-methyl-demethyloleuropein (3), have been isolated from the stem bark of Fraxinus chinensis, together with 23 known compounds (4-26). The structures of the new compounds were established by spectroscopic analyses (1D, 2D NMR, IR, UV, and HRESIMS). Among the isolated compounds, (8E)-4''-O-methylligstroside (1), (8E)-4''-O-methyldemethylligstroside (2), 3'',4''-di-O-methyldemethyloleuropein (3), oleuropein (6), aesculetin (9), isoscopoletin (11), aesculetin dimethyl ester (12), fraxetin (14), tyrosol (21), 4-hydroxyphenethyl acetate (22), and (+)-pinoresinol (24) exhibited inhibition (IC50 ≤ 7.65 µg/mL) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leuckyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 9, 11, 14, 21, and 22 inhibited fMLP/CB-induced elastase release with IC50 ≤ 3.23 µg/mL. In addition, compounds 2, 9, 11, 14, and 21 showed potent inhibition with IC50 values ≤ 27.11 µM, against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation. The well-known proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), were also inhibited by compounds 1, 9, and 14. Compounds 1, 9, and 14 displayed an anti-inflammatory effect against NO, TNF-α, and IL-6 through the inhibition of activation of MAPKs and IκBα in LPS-activated macrophages. In addition, compounds 1, 9, and 14 stimulated anti-inflammatory M2 phenotype by elevating the expression of arginase 1 and Krüppel-like factor 4 (KLF4). The above results suggested that compounds 1, 9, and 14 could be considered as potential compounds for further development of NO production-targeted anti-inflammatory agents.

Chemical Constituents with GNMT-Promoter-Enhancing and NRF2-Reduction Activities from Taiwan Agarwood Excoecaria formosana.

Hepatocellular carcinoma (HCC) is considered to be a silent killer, and was the fourth leading global cause of cancer deaths in 2018. For now, sorafenib is the only approved drug for advanced HCC treatment. The introduction of additional chemopreventive agents and/or adjuvant therapies may be helpful for the treatment of HCC. After screening 3000 methanolic extracts from the Formosan plant extract bank, Excoecaria formosana showed glycine N-methyltransferase (GNMT)-promoter-enhancing and nuclear factor erythroid 2-related factor 2 (NRF2)-suppressing activities. Further, the investigation of the whole plant of E. formosana led to the isolation of a new steroid, 7α-hydroperoxysitosterol-3-O-ß-d-(6-O-palmitoyl)glucopyranoside (1); two new coumarinolignans, excoecoumarin A (2) and excoecoumarin B (3); a new diterpene, excoeterpenol A (4); and 40 known compounds (5-44). Among them, Compounds 38 and 40-44 at a 100 µM concentration showed a 2.97 ± 0.27-, 3.17 ± 1.03-, 2.73 ± 0.23-, 2.63 ± 0.14-, 6.57 ± 0.13-, and 2.62 ± 0.05-fold increase in GNMT promoter activity, respectively. In addition, Compounds 40 and 43 could reduce NRF2 activity, a transcription factor associated with drug resistance, in Huh7 cells with relative activity of 33.1 ± 0.2% and 45.2 ± 2.5%. These results provided the basis for the utilization of Taiwan agarwood for the development of anti-HCC agents.

Two new diprenylated flavanones from Derris laxiflora Benth.

Phytochemical reinvestigation on the whole plants of Derris laxiflora Benth. afforded two new diprenylated flavanones, derriflavanones B and C (1-2), together with thirty-two known compounds, including sixteen flavonoids (3-18), eleven aromatic compounds (19-29), and five chlorophylls (30-34). All known compounds were first isolated from this plant. The structures of these compounds were determined by analysis of the NMR spectroscopy, mass data, IR spectra, UV spectra, optical rotation and by comparison with literature data.

Three New Iridoid Derivatives Have Been Isolated from the Stems of Neonauclea reticulata (Havil.) Merr. with Cytotoxic Activity on Hepatocellular Carcinoma Cells.

Three new iridoids, namely neonanin A (1), neonanin B (2) and neoretinin A (3), as well as twelve known compounds, 6-hydroxy-7-methyl-1-oxo-4-carbomethoxyoctahydrocyclopenta[c]pyran (4), 4-epi-alyxialactone (5), loganetin (6), loganin (7), phenylcoumaran-α'-aldehyde (8), cleomiscosin A (9), ficusal (10), balanophonin (11), vanillic acid (12), p-coumaric acid (13), cis,trans-abscisic acid (14), and trans,trans-abscisic acid (15) were isolated from the stems of Neonauclea reticulata (Havil.) Merr. These new structures were determined by the detailed analysis of spectroscopic data and comparison with the data of known analogues. Compounds 1⁻13 were evaluated using an in-vitro MTT cytotoxic assay for hepatocellular carcinoma (HCC) cells, and the preliminary results showed that ficusal (10), balanophonin (11), and p-coumaric acid (13) exhibited moderate cytotoxic activity, with EC50 values of 85.36 ± 4.36, 92.63 ± 1.41, and 29.18 ± 3.48 µg/mL against Hep3B cells, respectively.

Four New 2-(2-Phenylethyl)-4H-chromen-4-one Derivatives from the Resinous Wood of Aquilaria sinensis and Their Inhibitory Activities on Neutrophil Pro-Inflammatory Responses.

Four new 2-(2-phenylethyl)-4H-chromen-4-one derivatives, 6-hydroxy-5-methoxy-2-[2-(4'-methoxyphenyl)ethyl]chromone (1: ), 6,7-dimethoxy-2-[2-(2'-hydroxyphenyl)ethyl]chromone (2: ), 5-hydroxy-6-methoxy-2-[2-(3'-methoxyphenyl)ethyl]-chromone (3: ), and 7-chloro-8-hydroxy-2-[2-(4'-methoxyphenyl)ethyl]chromone (4: ), have been isolated from the resinous wood of Aquilaria sinensis, together with 16 known compounds (5: -20: ). Among these, 7-methoxy-2-[2-(4'-methoxyphenyl)ethyl]chromone (5: ) was isolated from a natural source for the first time. The structures of the new compounds were established by spectroscopic analyses (1D and 2D NMR, HR-ESI-MS, IR, UV). Nine compounds, including 1: showed more than 80% inhibition of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine at 50 µM.

New Benzenoid Derivatives and Other Constituents from Lawsonia inermis with Inhibitory Activity against NO Production.

Three new benzenoid derivatives, lawsoinermone (1), inermidioic acid (2), and inermic acid (3) have been isolated from the aerial part of Lawsonia inermis, together with 11 known compounds (4-14). The structures of three new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4-6, 13 and 14 were evaluated for inhibition of nitric oxide production in LPS-stimulated product of nitrite in RAW 264.7 cells with IC50 values of 6.12, 16.43, 18.98, 9.30, 9.30 and 14.90 µg/mL, respectively.

New Flavones, a 2-(2-Phenylethyl)-4H-chromen-4-one Derivative, and Anti-Inflammatory Constituents from the Stem Barks of Aquilaria sinensis.

In the current study, two new flavones, 4'-O-geranyltricin (1) and 3'-O-geranylpolloin (2), and a new 2-(2-phenylethyl)-4H-chromen-4-one derivative, 7-hydroxyl-6-methoxy-2-(2-phenylethyl)chromone (3), have been isolated from the stem barks of A. sinensis, together with 21 known compounds 4-24. The structures of new compounds 1-3 were determined through spectroscopic and MS analyses. Compounds 2, 3, 5, 6, and 8-10 exhibited inhibition (IC50≤12.51 µM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 3, 6, 8, 10, and 19 inhibited fMLP/CB-induced elastase release with IC50 values≤15.25 µM. This investigation reveals bioactive isolates (especially 2, 3, 5, 6, 8, 9, 10, and 19) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases.

New pterosin sesquiterpenes and antitubercular constituents from Pteris ensiformis.

Two new pterosin sesquiterpenes, (2S)-13-hydroxypterosin A (1) and (2S,3S)-12-hydroxypterosin Q (2), were isolated from the whole plants of Pteris ensiformis, together with six known compounds. The structures of 1 and 2 were determined through extensive 1D/2D-NMR and MS analyses. Compound 2 exhibited antitubercular activity (MIC 6.25 µg/ml) against Mycobacterium tuberculosis H37 Rv in vitro.

Phytochemical investigation of Annulohypoxylon ilanense, an endophytic fungus derived from Cinnamomum species.

Cultivation of the fungal strain Annulohypoxylon ilanense, an endophytic fungus isolated from the wood of medicinal plant Cinnamomum species, resulted in the isolation of one new furanoid derivative, ilanefuranone (1), one new pyrrole alkaloid, ilanepyrrolal (2), and one new biarylpropanoid derivative, ilanenoid (3), together with 22 known compounds, of which one α-tetralone analog, (-)-(4R)-3,4-dihydro-4,6-dihydroxynaphthalen-1(2H)-one (4) was isolated for the first time from a natural source. The structures were elucidated on the basis of physicochemical evidence, in-depth NMR spectroscopic analysis, and high-resolution mass spectrometry, and the antimycobacterial activities were also evaluated.

Secondary metabolites from the stems of Engelhardia roxburghiana and their antitubercular activities.

Bioassay-guided fractionation of stems of Engelhardia roxburghiana led to isolation of: four diarylheptanoids, engelheptanoxides A-D (1-4); two cyclic diarylheptanoids, engelhardiols A (5) and B (6); one naphthoquinone dimer, engelharquinonol (7); and one 1-tetralone, (4S)-4,6-dihydroxy-1-tetralone (8), along with 24 known compounds (9-32). The structures of 1-8 were by spectroscopic analysis. Compounds 5, 6, 13, 22, and 23 showed antitubercular activity against Mycobacterium tuberculosis H(37)Rv with MIC values of 72.7, 62.1, 9.1, 15.3, and 70.1µM, respectively.

Orthoquinone and naphthalenone derivatives from Berrya ammonilla and their anti-inflammatory activity.

A new orthoquinone, berryammone A (1), and four new naphthalenone derivatives, berryammone B (2), berryammone C (3), 6-O-methylberryammone C (4), and 4-O-methylberryammone C (5), have been isolated from the stem of Berrya ammonilla, together with eleven known compounds (6-16). The structures of these new compounds were determined through spectroscopic and MS analyses. Among the isolates, compounds 1-3, 5, (+)-pinoresinol (6), and betulinic acid (12) exhibited inhibition (IC50 ≤ 4.41 µM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 2, and 5 also inhibited fMLP/CB-induced elastase release with IC50 values ≤ 3.95 µM.