Anti-inflammatory butanolides and lignanoids from the root of Machilus zuihoensis var. mushaensis.

From the anti-inflammatory screening of Formosan Lauraceous plants, the methanolic extract of the root of Machilus zuihoensis var. mushaensis stood out for its potent inhibitory activity toward superoxide anion and elastase release in human neutrophils. Bioassay-guided fractionation of the root of M. zuihoensis var. mushaensis led to eight new compounds, including two butanolides (1-2), five lignanoids (3-7), and one sesquiterpenoid (8), along with 50 known compounds (9-58). Structures of these compounds were elucidated by NMR, UV, IR, CD, and MS analyses. Thirty-two isolates were evaluated for their anti-inflammatory activity. Among them, 9, 20, 27, 28, 30, 31, 35, and 40 exhibited significant superoxide anion generation inhibition selectively (IC50 value < 7.4 µM), 15 and 19 showed selective inhibition toward elastase release (IC50 value < 8.0 µM). Moreover, 3, 16, 21, and 22 simultaneously displayed superoxide anion generation and elastase release inhibition. It is worth mentioning that 21 and 22 showed more potent inhibitory activities (IC50 < 1.0 µM) on superoxide anion than the positive control, LY294002. Further quantitative HPLC analysis indicated the content of 21 and 22 were 0.90 and 3.04 mg/g (w/w) in the ethyl-acetate layer of the root of M. zuihoensis var. mushaensis, respectively. Altogether, M. zuihoensis var. mushaensis revealed a potential for developing the botanical new drug against inflammation-related disease.

Towards Sustainable Medicinal Resources through Marine Soft Coral Aquaculture: Insights into the Chemical Diversity and the Biological Potential.

In recent decades, aquaculture techniques for soft corals have made remarkable progress in terms of conditions and productivity. Researchers have been able to obtain larger quantities of soft corals, thus larger quantities of biologically active metabolites, allowing them to study their biological activity in many pharmacological assays and even produce sufficient quantities for clinical trials. In this review, we summarize 201 secondary metabolites that have been identified from cultured soft corals in the era from 2002 to September 2022. Various types of diterpenes (eunicellins, cembranes, spatanes, norcembranes, briaranes, and aquarianes), as well as biscembranes, sterols, and quinones were discovered and subjected to bioactivity investigations in 53 different studies. We also introduce a more in-depth discussion of the potential biological effects (anti-cancer, anti-inflammatory, and anti-microbial) and the mechanisms of action of the identified secondary metabolites. We hope this review will shed light on the untapped potential applications of aquaculture to produce valuable secondary metabolites to tackle current and emerging health conditions.

Phytochemical Investigation and Anti-Inflammatory Activity of the Leaves of Machilus japonica var. kusanoi.

In a series of anti-inflammatory screenings of lauraceous plants, the methanolic extract of the leaves of Machilus japonica var. kusanoi (Hayata) J.C. Liao showed potent inhibition on both superoxide anion generation and elastase release in human neutrophils. Bioassay-guided fractionation of the leaves of M. japonica var. kusanoi led to the isolation of twenty compounds, including six new butanolides, machinolides A-F (1-6), and fourteen known compounds (7-20). Their structures were characterized by 1D and 2D NMR, UV, IR, CD, and MS data. The absolute configuration of the new compounds were unambiguously confirmed by single-crystal X-ray diffraction analyses (1, 2, and 3) and Mosher's method (4, 5, and 6). In addition, lignans, (+)-eudesmin (11), (+)-methylpiperitol (12), (+)-pinoresinol (13), and (+)-galbelgin (16) exhibited inhibitory effects on N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation in human neutrophils with IC50 values of 8.71 ± 0.74 µM, 2.23 ± 0.92 µM, 6.81 ± 1.07 µM, and 7.15 ± 2.26 µM, respectively. The results revealed the anti-inflammatory potentials of Formosan Machilus japonica var. kusanoi.

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.

Anti-Inflammatory and Antibacterial Activity Constituents from the Stem of Cinnamomum validinerve.

One new dibenzocycloheptene, validinol (1), and one butanolide firstly isolated from the natural source, validinolide (2), together with 17 known compounds were isolated from the stem of Cinnamomum validinerve. Among the isolates, lincomolide A (3), secosubamolide (7), and cinnamtannin B1 (19) exhibited potent inhibition on both superoxide anion generation (IC50 values of 2.98 ± 0.3 µM, 4.37 ± 0.38 µM, and 2.20 ± 0.3 µM, respectively) and elastase release (IC50 values of 3.96 ± 0.31 µM, 3.04 ± 0.23 µM, and 4.64 ± 0.71 µM, respectively) by human neutrophils. In addition, isophilippinolide A (6), secosubamolide (7), and cinnamtannin B1 (19) showed bacteriostatic effects against Propionibacterium acnes in in vitro study, with minimal inhibitory concentration (MIC) values at 16 µg/mL, 16 µg/mL, and 500 µg/mL, respectively. Further investigations using the in vivo ear P. acnes infection model showed that the intraperitoneal administration of the major component cinnamtannin B1 (19) reduced immune cell infiltration and pro-inflammatory cytokines TNF-α and IL-6 at the infection sites. The results demonstrated the potential of cinnamtannin B1 (19) for acne therapy. In summary, these results demonstrated the anti-inflammatory potentials of Formosan C. validinerve during bacterial infections.

High-Content Screening of a Taiwanese Indigenous Plant Extract Library Identifies Syzygium simile leaf Extract as an Inhibitor of Fatty Acid Uptake.

Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in the recent decades in both developed and developing countries, and is predicted to be the major etiology for liver transplantation in the next decade. Thus, pharmacological strategies to treat NAFLD are urgently needed. Natural products are considered an excellent source for drug discovery. By utilizing an image-based high-throughput screening with a library containing 3000 Taiwanese indigenous plant extracts, we discovered that the extract of Syzygium simile leaves (SSLE) has an anti-lipid droplet (LD) accumulation effect in hepatic cell lines. Analyses of the expression profile of genes involved in lipid metabolism revealed that SSLE suppressed the mRNA expression of CD36, fatty acid translocase. In agreement with this observation, we showed that SSLE inhibited CD36 protein expression and fatty acid uptake and has only limited effects on pre-formed LDs. Moreover, SSLE reduced LD accumulation and CD36 expression in enterocyte and macrophage cell lines. In conclusion, our findings suggest that SSLE could serve as a potential source for the discovery of novel therapeutic modalities for NAFLD and that the suppression of CD36 expression and fatty acid uptake could contribute to the lipid-lowering effect of SSLE.

Secondary Metabolites of the Endophytic Fungus Lachnum abnorme from Ardisia cornudentata.

Fractionation of an EtOAc-soluble fraction of the solid fermentate of an endophytic fungus, Lachnum abnorme Mont. BCRC 09F0006, derived from the endemic plant, Ardisia cornudentata Mez. (Myrsinaceae), resulted in the isolation of three new chromones, lachnochromonins D-F (1-3), one novel compound, lachabnormic acid (4), along with nine known compounds (5-13). Their structures were elucidated by spectroscopic analyses. Alternariol-3,9-dimethyl ether (6) was given the correct data as well as 2D spectral analyses for the first time. This is the first report of the isolation of one unprecedented compound 4 from Lachnum genus, while all known compounds were also found for the first time from Lachnum. The effects of some isolates (3, 4, 7-9, 10, and 13) on the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophages were also evaluated. Several compounds exhibited weak inhibitory activity on lipopolysaccharide (LPS)-stimulated NO production in RAW 264.7 macrophages.

Anti-inflammatory constituents from a sea anemone-derived fungus Arthrinium arundinis MA30.

In this study, preliminary field-sampling of bioactive fungal strains and bioassay-guided selection were conducted. A number of fungal strains were isolated from sea anemones along the northeastern coast of Badouzi, Keelung, Taiwan. Among them, Arthrinium arundinis MA30 showed significant anti-inflammatory activity and was thus selected for further chemical investigation. After a series of purification and isolation using different chromatographic techniques on the fermented products of A. arundinis MA30, thirty-one compounds were identified, five of which were previously unreported, including arthrinoic acid, hexylaconitic anhydride methyl ester, (3S,8R)-8-hydroxy-3-carboxy-2-methylenenonanoic acid, and arthripenoids G and H. These compounds were subjected to comprehensive spectroscopic data analysis. Of all the isolates, 1,3,5,6-tetrahydroxy-8-methylxanthone and arthripenoid C demonstrated the most distinctive inhibitory activities against nitric oxide production in mouse microglial BV-2 cells, with their respective inhibitory rates being 71% and 81% at 10 µM concentration, and their respective IC50 values were further determined to be 5.3 ± 0.6 and 1.6 ± 0.4 µM. These compounds showed no significant cytotoxicity, and curcumin was used as a positive control in this study.

The SAR analysis of dietary polyphenols and their antagonistic effects on bortezomib at physiological concentrations.

Background: Bortezomib (BTZ), a primary treatment for MM, but its effectiveness can be reduced by interactions with vicinal diol moieties (VDMs) in polyphenols. Despite this, it's debated whether BTZ therapy necessitates avoiding polyphenol-rich products, given the low bioavailability of polyphenols. Additionally, it remains unclear whether the structure of polyphenols contributes to their BTZ antagonism. Therefore, our study aims to unravel the structure-activity relationship of dietary polyphenols and their BTZ antagonism at daily diet-achievable physiological concentrations. Methods: We assessed the antagonistic effects of 25 polyphenols against BTZ using cell viability assays in RPMI 8226 cells. ChemGPS-NP helped analyze the structural similarity. Additionally, long-term cytotoxicity assays evaluated these effects at physiologically relevant concentrations. Results: By cell viability assays, we found a positive correlation between the number of VDMs in gallotannins and their BTZ antagonism. Moreover, the origin and configuration of VDMs, rather than the total VDM concentration, play a pivotal role in the combined antagonistic effects against BTZ in gallotannins. Additionally, ChemGPS-NP analysis indicated that the aromaticity and C-3 hydroxyl group in flavonoids' C-rings enhance their BTZ antagonism. Finally, long-term cytotoxicity assays reveal that gallic acid (GA), epigallocatechin (EGC), and epigallocatechin gallate (EGCG), at their physiological concentrations-attainable through tea consumption-significantly and synergistically antagonize BTZ. Conclusion: Due to the potential for these polyphenols to reduce the effectiveness of BTZ, it is advisable for MM patients undergoing BTZ treatment to reduce their consumption of foods high in VDM-containing polyphenols.

Chemical investigations and cytotoxic effects of metabolites from Antrodia camphorata against human hepatocellular carcinoma cells.

Antrodia camphorata is used as a medicinal fungus in Taiwan to treat fatigue, food intoxication, and enhance liver function. Here we identified fermented metabolic components from the mycelium of A. camphorata KH37 and explored their anti-hepatoma potentials with study models of human hepatoblastoma cell lines. Bioassay-guided fractionation of the solid fermentation powder of A. camphorata KH37 led to the isolation of one new quinonol, antroquinonol Z (1), and nine known compounds (2-10). Treatment with 10 µM antrocamols LT1 (2) or LT3 (3) reduced cell viability of HepG2 and Huh-7 cells to about 60% in 48 hours. Antroquinonol Z (1) exhibited mild cytotoxicity against Huh-7 cells in 48 and 72 hours. Interestingly, two fractions showed cytotoxicity in HepG2 and Huh-7 cells, even better than compounds isolated from these fractions. The significant cytotoxicity of partially purified samples from A. camphorata KH37 exhibited a potential for developing alternative or complementary therapeutics against hepatoma.

Chemical Constituents with Anti-Lipid Droplet Accumulation and Anti-Inflammatory Activity from Elaeagnus glabra.

Non-alcoholic fatty liver disease (NAFLD) is a type of steatosis caused by excess lipids accumulating in the liver. The prevalence of NAFLD has increased annually due to modern lifestyles and a lack of adequate medical treatment. Thus, we were motivated to investigate the bioactive components of Formosan plants that could attenuate lipid droplet (LD) accumulation. In a series of screenings of 3000 methanolic extracts from the Formosan plant extract bank for anti-LD accumulation activity, the methanolic extract of aerial parts of Elaeagnus glabra Thunb. showed excellent anti-LD accumulation activity. E. glabra is an evergreen shrub on which only a few phytochemical and biological studies have been conducted. Here, one new flavonoid (1), two new triterpenoids (2 and 3), and 35 known compounds (4-38) were isolated from the ethyl acetate layer of aerial parts of E. glabra via a bioassay-guided fractionation process. Their structures were characterized by 1D and 2D NMR, UV, IR, and MS data. Among the isolated compounds, methyl pheophorbide a (37) efficiently reduced the normalized LD content to 0.3% with a concentration of 20 µM in AML12 cell lines without significant cytotoxic effects. 3-O-(E)-Caffeoyloleanolic acid (13) and methyl pheophorbide a (37) showed inhibitory effects on superoxide anion generation or elastase release in fMLP/CB-treated human neutrophils (IC50 < 3.0 µM); they displayed effects similar to those of the positive control, namely, LY294002. These findings indicate that E. glabra can be used for developing a new botanical drug for managing LD accumulation and against inflammation-related diseases.

In vitro and in silico studies of 7'',8''-buddlenol D anti-inflammatory lignans from Carallia brachiata as p38 MAP kinase inhibitors.

Excessive macrophage activation induces the release of high levels of inflammatory mediators which not only amplify chronic inflammation and degenerative diseases but also exacerbate fever and retard wound healing. To identify anti-inflammatory molecules, we examined Carallia brachiata-a medicinal terrestrial plant from Rhizophoraceae. Furofuran lignans [(-)-(7''R,8''S)-buddlenol D (1) and (-)-(7''S,8''S)-buddlenol D (2)] isolated from the stem and bark inhibited nitric oxide (half maximal inhibitory concentration (IC50): 9.25 ± 2.69 and 8.43 ± 1.20 micromolar for 1 and 2, respectively) and prostaglandin E2 (IC50: 6.15 ± 0.39 and 5.70 ± 0.97 micromolar for 1 and 2, respectively) productions in lipopolysaccharide-induced RAW264.7 cells. From western blotting, 1 and 2 suppressed LPS-induced inducible nitric oxide synthase and cyclooxygenase-2 expression in a dose-dependent manner (0.3-30 micromolar). Moreover, analysis of the mitogen-activated protein kinase (MAPK) signaling pathway showed decreased p38 phosphorylation levels in 1- and 2-treated cells, while phosphorylated ERK1/2 and JNK levels were unaffected. This discovery agreed with in silico studies which suggested 1 and 2 bound to the ATP-binding site in p38-alpha MAPK based on predicted binding affinity and intermolecular interaction docking. In summary, 7'',8''-buddlenol D epimers demonstrated anti-inflammatory activities via p38 MAPK inhibition and may be used as viable anti-inflammatory therapies.

Anti-Lymphangiogenic Terpenoids from the Heartwood of Taiwan Juniper, Juniperus chinensis var. tsukusiensis.

To look in-depth into the phytochemical and pharmacological properties of Taiwan juniper, this study investigated the chemical profiles and anti-lymphangiogenic activity of Juniperus chinensis var. tsukusiensis. In this study, four new sesquiterpenes, 12-acetoxywiddrol (1), cedrol-13-al (2), α-corocalen-15-oic acid (3), 1,3,5-bisaoltrien-10-hydroperoxy-11-ol (4), one new diterpene, 1ß,2ß-epoxy-9α-hydroxy-8(14),11-totaradiene-3,13-dione (5), and thirty-three known terpenoids were successfully isolated from the heartwood of J. chinensis var. tsukusiensis. The structures of all isolates were determined through the analysis of physical data (including appearance, UV, IR, and optical rotation) and spectroscopic data (including 1D, 2D NMR, and HRESIMS). Thirty-four compounds were evaluated for their anti-lymphangiogenic effects in human lymphatic endothelial cells (LECs). Among them, totarolone (6) displayed the most potent anti-lymphangiogenic activity by suppressing cell growth (IC50 = 6 ± 1 µM) of LECs. Moreover, 3ß-hydroxytotarol (7), 7-oxototarol (8), and 1-oxo-3ß-hydroxytotarol (9) showed moderate growth-inhibitory effects on LECs with IC50 values of 29 ± 1, 28 ± 1, and 45 ± 2 µM, respectively. Totarolone (6) also induced a significant concentration-dependent inhibition of LEC tube formation (IC50 = 9.3 ± 2.5 µM) without cytotoxicity. The structure-activity relationship discussion of aromatic totarane-type diterpenes against lymphangiogenesis of LECs is also included in this study. Altogether, our findings unveiled the promising potential of J. chinensis var. tsukusiensis in developing therapeutics targeting tumor lymphangiogenesis.

Chemical Constituents and Bioactive Principles from the Mexican Truffle and Fermented Products of the Derived Fungus Ustilago maydis MZ496986.

To look in-depth into the traditional Mexican truffle, this study investigated the phytochemical and pharmacological properties of field-collected corn galls and the fermentate of its pathogen Ustilago maydis MZ496986. Here, we established the chemical profiles of both materials via the gradient HPLC-UV method and successfully identified six previously unreported chemical entities, ustilagols A-F (1-6), and 17 known components. Compounds 3, 5, and 9 exhibited potent nitric oxide production inhibitory activities in murine brain microglial BV-2 cells (IC50 = 6.7 ± 0.5, 5.8 ± 0.9, and 3.9 ± 0.1 µM) without cytotoxic effects. DIMBOA (9) also attenuates lipopolysaccharide (LPS)-stimulated NF-κB activation in RAW 264.7 macrophages (IC50 = 58.1 ± 7.2 µM). Ustilagol G (7) showed potent antiplatelet aggregation in U46619-stimulated human platelets (IC50 = 16.5 ± 5.3 µM). These findings highlighted the potential of corn galls and U. maydis MZ496986 fermentate as functional foods for improving inflammation-related discomforts and vascular obstruction.

Prinsepiae Nux Extract Activates NRF2 Activity and Protects UVB-Induced Damage in Keratinocyte.

Ultraviolet B (UVB) is one of the most important environmental factors that cause extrinsic aging through increasing intracellular reactive oxygen species (ROS) production in the skin. Due to its protective roles against oxidative stress, nuclear factor erythroid-2-related factor (NRF2) has been traditionally considered as a target for skin aging prevention. Here, we identified the extract of Prinsepiae Nux, a top-grade drug listed in Shen Nong Ben Cao Jing, as a potent NRF2 activator by high-throughput screening. A bioassay-guided fractionation experiment revealed that NRF2-activating components were concentrated in the 90% methanol (MP) fraction. MP fraction significantly increased the expression of NRF2 and HO-1 protein and upregulated HO-1 and NQO1 mRNA expression in HaCaT cells. Moreover, MP fraction pre-treatment dramatically reversed UVB-induced depletion of NRF2 and HO-1, accumulation of intracellular ROS, NF-κB activation, and the upregulation of pro-inflammatory genes. Finally, the qualitative analysis using UPLC-tandem mass spectroscopy revealed the most abundant ion peak in MP fraction was identified as α-linolenic acid, which was further proved to activate NRF2 signaling. Altogether, the molecular evidence suggested that MP fraction has the potential to be an excellent source for the discovery of natural medicine to treat/prevent UVB-induced skin damage.

The Potential Implications of Hydrogen Sulfide in Aging and Age-Related Diseases through the Lens of Mitohormesis.

The growing increases in the global life expectancy and the incidence of chronic diseases as a direct consequence have highlighted a demand to develop effective strategies for promoting the health of the aging population. Understanding conserved mechanisms of aging across species is believed helpful for the development of approaches to delay the progression of aging and the onset of age-related diseases. Mitochondrial hormesis (or mitohormesis), which can be defined as an evolutionary-based adaptive response to low-level stress, is emerging as a promising paradigm in the field of anti-aging. Depending on the severity of the perceived stress, there are varying levels of hormetic response existing in the mitochondria called mitochondrial stress response. Hydrogen sulfide (H2S) is a volatile, flammable, and toxic gas, with a characteristic odor of rotten eggs. However, H2S is now recognized an important gaseous signaling molecule to both physiology and pathophysiology in biological systems. Recent studies that elucidate the importance of H2S as a therapeutic molecule has suggested its protective effects beyond the traditional understanding of its antioxidant properties. H2S can also be crucial for the activation of mitochondrial stress response, postulating a potential mechanism for combating aging and age-related diseases. Therefore, this review focuses on highlighting the involvement of H2S and its sulfur-containing derivatives in the induction of mitochondrial stress response, suggesting a novel possibility of mitohormesis through which this gaseous signaling molecule may promote the healthspan and lifespan of an organism.

Chemical constituents and their anti-neuroinflammatory activities from the bark of Taiwan incense cedar, Calocedrus formosana.

One undescribed C40 terpenoid, calomacroquinoic acid; four undescribed diterpenes, 5α,6α-epoxy-7α-hydroxyferruginol, 15-ethoxysugiol, 7-methoxy-6,7-secoabieta-8,11,13-triene-6,12-diol, and ethyl 7,8-secoabieta-11,14-dioxo-7-ate; two compounds isolated from Nature for the first time, 6ß,7α-dihydroxyferruginol and 12-O-methyltaxochinon; and six known compounds were successfully identified from the bark of Taiwan incense cedar Calocedrus formosana. Structures of all isolates were elucidated by physical data (appearance, ultraviolet, infrared, specific rotation, and X-ray) and spectroscopic data (1D and 2D nuclear magnetic resonance, and high-resolution electron ionization mass spectrometry). The biosynthetic pathway of calomacroquinoic acid is also described in the current study. Nitric oxide production in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells was inhibited by 6,7-dehydroferruginol, 7α,11-dihydroxy-12-methoxy-8,11,13-abietriene, and trans-communic acid. Altogether, the bark of C. formosana possessed several potential natural therapeutics against inflammation-related neuronal diseases.

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.

Investigations into Chemical Components from Monascus purpureus with Photoprotective and Anti-Melanogenic Activities.

Monascus species are asexually or sexually reproduced homothallic fungi that can produce a red colorant, specifically the so-called red yeast rice or Anka, which is used as a food ingredient in Asia. Traditional experiences of using Monascus for treating indigestion, enhancing blood circulation, and health remedies motivate us to investigate and repurpose Monascus-fermented products. Here, two new 5H-cyclopenta[c]pyridine type azaphilones, 5S,6S-monaspurpyridine A (1) and 5R,6R-monaspurpyridine A (2), two new xanthonoids, monasxanthones A and B (3 and 4), one new naphthalenone, monasnaphthalenone (5), and one new azaphilone, monapurpurin (6), along with two known compounds were isolated from the 70% EtOH extract of a citrinin-free domesticated strain M. purpureus BCRC 38110. The phytochemical properties of the xanthonoid and naphthalenone components were first identified from Monascus sp. differently from the representative ingredients of polyketide-derived azaphilones. UVB-induced cell viability loss and reactive oxygen species (ROS) overproduction in human keratinocytes were attenuated by monascuspirolide B (7) and ergosterol peroxide (8), indicating their photoprotective potentials. Ergosterol peroxide (8) decreased the melanin contents and tyrosinase activities of mouse melanocytes, depending on the concentration, suggesting their anti-melanogenic effects. In conclusion, six new and two known compounds were isolated from M. purpureus BCRC 38110, and two of them exhibited dermal protective activities. The results revealed the novel potential of M. purpureus for developing natural cosmeceutics against skin photoaging.

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.