Ruta graveolens: Boost Melanogenic Effects and Protection against Oxidative Damage in Melanocytes.

Vitiligo, an acquired depigmentation disorder, is characterized by the loss of functional melanocytes and epidermal melanin. In recent years, research has focused on promoting melanin biosynthesis and protecting melanocytes to reduce stress-related damage for the purpose of applying it to vitiligo treatment. Ruta graveolens L. has been utilized as a medicinal herb in diverse traditional medicine systems to address conditions like vitiligo. In this investigation, we isolated and purified 16 unique alkaloid compounds from the chloroform extracts of R. graveolens, encompassing a new quinoline alkaloid and several recognized compounds. Bioactivity analysis showed that compound 13, an alkaloid derived from R. graveolens, promotes melanin production while protecting PIG3V melanocytes against 4-tert-butylphenol (4-TBP)-induced oxidative damage by downregulating endoplasmic reticulum (ER) stress and pro-inflammatory cytokines through interleukin-6 (IL-6) regulation. Additionally, the compound suppressed the expression of Bip, IRE1, p-IRE1, and XBP-1 proteins, suggesting a potential antioxidant function. These findings suggest that compound 13 isolated from R. graveolens can augment melanogenesis in melanocytes, reduce endoplasmic reticulum (ER) stress, and ameliorate vitiligo exacerbation. The melanogenic activity observed in the chloroform fraction emphasizes R. graveolens's potential as a novel therapeutic target for vitiligo treatment, warranting further exploration in future studies.

Quercetin 3-O-(6″-O-E-caffeoyl)-ß-D-glucopyranoside, a Flavonoid Compound, Promotes Melanogenesis through the Upregulation of MAPKs and Akt/GSK3ß/ß-Catenin Signaling Pathways.

Quercetin 3-O-(6″-O-E-caffeoyl)-ß-D-glucopyranoside is a flavonoid compound produced by various plants with reported antiprotozoal potential against E. histolytica and G. lamblia; however, its effects on skin pigment regulation have not been studied in detail. In this investigation, we discovered that quercetin 3-O-(6″-O-E-caffeoyl)-D-glucopyranoside (coded as CC7) demonstrated a more increased melanogenesis effect in B16 cells. CC7 exhibited no cytotoxicity or effective stimulating melanin content or intracellular tyrosinase activity. This melanogenic-promoting effect was accompanied by activated expression levels of microphthalmia-associated transcription factor (MITF), a key melanogenic regulatory factor, melanogenic enzymes, and tyrosinase (TYR) and tyrosinase-related protein-1 (TRP-1) and 2 (TRP-2) in the CC7-treated cells. Mechanistically, we found that CC7 exerted melanogenic effects by upregulating the phosphorylation of stress-regulated protein kinase (p38) and c-Jun N-terminal kinase (JNK). Moreover, the CC7 upregulation of phosphor-protein kinase B (Akt) and Glycogen synthase kinase-3 beta (GSK-3ß) increased the content of ß-catenin in the cell cytoplasm, and subsequently, it translocated into the nucleus, resulting in melanogenesis. Specific inhibitors of P38, JNK, and Akt validated that CC7 promotes melanin synthesis and tyrosinase activity by regulating the GSK3ß/ß-catenin signaling pathways. Our results support that the CC7 regulation of melanogenesis involves MAPKs and Akt/GSK3ß/ß-catenin signaling pathways.

Total flavonoid extract from Dracocephalum moldavica L. improves pulmonary fibrosis by reducing inflammation and inhibiting the hedgehog signaling pathway.

Dracocephalum Moldavica L. is a traditional herb for improving pharynx and relieving cough. However, the effect on pulmonary fibrosis is not clear. In this study, we explored the impact and molecular mechanism of total flavonoid extract from Dracocephalum moldavica L. (TFDM) on bleomycin-induced pulmonary fibrosis mouse model. Lung function testing, lung inflammation and fibrosis, and the related factors were detected by the lung function analysis system, HE and Masson staining, ELISA, respectively. The expression of proteins was studied through Western Blot, immunohistochemistry, and immunofluorescence while the expression of genes was analyzed by RT-PCR. The results showed that TFDM significantly improved lung function in mice, reduced the content of inflammatory factors, thereby reducing the inflammation. It was found that expression of collagen type I, fibronectin, and α-smooth muscle actin was significantly decreased by TFDM. The results further showed that TFDM interferes with hedgehog signaling pathway by decreasing the expression of Shh, Ptch1, and SMO proteins and thereby inhibiting the generation of downstream target gene Gli1 and thus improving pulmonary fibrosis. Conclusively, these findings suggest that TFDM improve pulmonary fibrosis by reducing inflammation and inhibition of the hedgehog signaling pathway.

Pyrrolizidine alkaloids from Jacobaea vulgaris Gaertn and theoretical studies on intramolecular interactions.

Two undescribed pyrrolizidine alkaloids, 13-dehydrosenkirkine (1) and chloromethylretrorsine (2), along with three known analogues, onetine (3), retrorsine (4), and usaramine N-oxide (5), were isolated from Jacobaea vulgaris Gaertn. The structures of the undescribed compounds were elucidated by extensive spectrometric and spectroscopic techniques, including HRESIMS, NMR, calculated 13C-NMR DP4+ analysis and comparison with experimental and calculated ECD spectra. The undescribed compounds were evaluated for their antitumour activity against HT29, HeLa, and HepG2 cells. In addition, the intramolecular interactions and quadrupolar couplings were revealed by investigating the geometrical and electronic properties of three typical otonecine-type PAs in DFT theory.

Sesquiterpenoids from Seriphidium transiliense and Their Melanogenic Activity.

A sesquiterpenoid with an unprecedented 5/5/4 tricyclic skeleton (1), a nor-sesquiterpenoid with a rare 6/7 bicyclic skeleton (2), 10 new sesquiterpenoids (3-12), and six known analogues (13-18) were isolated from the whole plants of Seriphidium transiliense. The structures of compounds 1-12 were elucidated by spectroscopic data analysis. Compound 7 showed melanogenic promotion activity in murine melanoma (B16) cells more potent than the positive control used, 8-methoxypsoralen (8-MOP). Further mechanistic studies indicated that compound 7 promotes melanogenesis through activating the transcription of microphthalmia-associated transcription factor (MITF) and tyrosinase family genes in B16 cells. Moreover, compound 7 also inhibited the expression of IFN-γ-chemokine through the JAK/STAT signaling pathway in immortalized human keratinocyte (HaCaT) cells. These results suggest that the sesquiterpenoid 7 shows potential activity for treating vitiligo.

Guaianolides and unusual 3-oxa-guaianolides from Artemisia macrocephala.

Eight undescribed guaianolides (macrocephalolides A-H) and two known analogues (parishin C, artabsinolide E) were isolated from the whole plant of Artemisia macrocephala growing in Xinjiang, China. Their structures were determined on the basis of extensive spectroscopic analysis, with absolute configurations established by comparison of experimental and calculated ECD data, as well as confirmation of single-crystal X-ray diffraction crystallography. Macrocephalolides A-B featured an unusual type of 3-oxa-guaianolide with a cyclopentenone moiety. Macrocephalolides C-E possessed a dihydro-2H-pyran acetal segment, representing an unprecedented 2, 3-secoguaianolide skeleton with 6/7/5 tricyclic ring system in natural sesquiterpenes. The X-ray crystal structures of parishin C and artabsinolide E were reported for the first time.

Pyrrolizidine alkaloids and unusual millingtojanine A-B from Jacobaea vulgaris (syn. Senecio jacobaea L.).

Four undescribed pyrrolizidine alkaloids (seneciojanine A-D), two enantiomeric pairs of unusual alkaloids (millingtojanine A-B) with a unique tricyclic core, and nine known pyrrolizidine alkaloids were isolated from whole plant extracts of Jacobaea vulgaris Gaertn. The structures of the undescribed compounds were established by extensive spectroscopic and spectrometric analyses and comparison of theoretical and experimental ECD data. Several of the structures were also confirmed by X-ray diffraction analysis. Seneciojanine A-D possess a rare natural necine moiety with an α,ß-unsaturated carbonyl group located at C-3 and a hydroxyl substituent at C-8.

Rational Design of Hierarchical, Porous, Co-Supported, N-Doped Carbon Architectures as Electrocatalyst for Oxygen Reduction.

Developing highly active nonprecious-metal catalysts for the oxygen reduction reaction (ORR) is of great significance for reducing the cost of fuel cells. 3D-ordered porous structures could substantially improve the performance of the catalysts because of their excellent mass-diffusion properties and high specific surface areas. Herein, ordered porous ZIF-67 was prepared by forced molding of a polystyrene template, and Co-supported, N-doped, 3D-ordered porous carbon (Co-NOPC) was obtained after further carbonization. Co-NOPC exhibited excellent performance for the ORR in an alkaline medium with a half-wave potential of 0.86 V vs. reversible hydrogen electrode (RHE), which is higher than that of the state-of-the-art Pt/C (0.85 V vs. RHE). Moreover, the substantially improved catalytic performance of Co-NOPC compared with Co-supported, N-doped carbon revealed the key role of its hierarchical porosity in boosting the ORR. Co-NOPC also exhibited a close-to-ideal four-electron transfer path, long-term durability, and resistance to methanol penetration, which make it promising for large-scale application.

Piperidine Alkaloids with Diverse Skeletons from Anacyclus pyrethrum.

Fifteen new piperidine derivatives, pyracyclumines A-J (1-10), including five pairs of enantiomers, (+)-1/(-)-1 to (+)-5/(-)-5, together with three known compounds, agrocybenine (11), 4,6,6-trimethyl-5,6-dihydro-2(1 H)-pyridone (12), and 3,5,5-trimethyl-1,5-dihydro-2 H-pyrrol-2-one (13), were isolated from the roots of Anacyclus pyrethrum. Pyracyclumines A, B, and H (1, 2, and 8) possess a novel 6/5/6/6 dimeric piperidine skeleton, a unique 6/5/6 dimeric piperidine skeleton, and a 1,4,6-triazaindan skeleton, respectively. Pyracyclumine C (3) is based on a rare cyclopentane-piperidine framework. The structures of the isolated compounds were established by analysis of their NMR and HRESIMS data. The racemic pyracyclumines A-E (1-5) were further separated by chiral HPLC to give the enantiomers (+)-1/(-)-1 to (+)-5/(-)-5, for which the absolute configurations were determined by comparison of their experimental and calculated ECD spectra. The plausible biogenetic pathways of these piperidine alkaloids were proposed starting from the basic units of compounds 12 and 13. All of the isolated compounds were tested for their inhibitory effects on menin-mixed lineage leukemia 1 protein-protein interaction.

Urinary metabonomics study of anti-depressive effect of Chaihu-Shu-Gan-San on an experimental model of depression induced by chronic variable stress in rats.

Chaihu-Shu-Gan-San (CSGS), a traditional Chinese medicine (TCM) formula, has been effectively used for the treatment of depression in clinic. However, studies of its anti-depressive mechanism are challenging, accounted for the complex pathophysiology of depression, and complexity of CSGS with multiple constituents acting on different metabolic pathways. The variations of endogenous metabolites in rat model of depression after administration of CSGS may offer deeper insights into the anti-depressive effect and mechanism of CSGS. In this study, metabonomics based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) was used to profile the metabolic fingerprints of urine obtained from chronic variable stress (CVS)-induced depression model in rats with and without CSGS treatment. Through partial least squares-discriminate analysis, it was observed that metabolic perturbations induced by chronic variable stress were restored in a time-dependent pattern after treatment with CSGS. Metabolites with significant changes induced by CVS, including 3-O-methyldopa (1), pantothenic acid (2), kynurenic acid (3), xanthurenic acid (4), 2,8-dihydroxyquinoline glucuronide (5), 5-hydroxy-6-methoxyindole glucurnoide (8), l-phenylalanyl-l-hydroxyproline (9), indole-3-carboxylic acid (10), proline (11), and the unidentified metabolites (6, 2.11min_m/z 217.0940; 7, 2.11min_m/z 144.0799), were characterized as potential biomarkers involved in the pathogenesis of depression. The derivations of all those biomarkers can be regulated by CSGS treatment except indole-3-carboxylic acid (10), which suggested that the therapeutic effect of CSGS on depression may involve in regulating the dysfunctions of energy metabolism, tryptophan metabolism, bone loss and liver detoxification. This study indicated that the rapid and noninvasive urinary metabonomics approach may be a powerful tool to study the efficacy and mechanism of complex TCM prescriptions.

Laevigatbenzoate from Croton laevigatus Vahl.

A new trans-clerodane diterpenoid, laevigatbenzoate (1), was isolated from the leaves of Croton laevigatus Vahl. Its structure was established on the basis of spectroscopic analysis, and the absolute configuration was determined by application of the CD excitation chirality method. This compound showed weak cytotoxicity against HeLa cells, with an IC(50) value of 45.4 µM.

Online identification of the antioxidant constituents of traditional Chinese medicine formula Chaihu-Shu-Gan-San by LC-LTQ-Orbitrap mass spectrometry and microplate spectrophotometer.

Chaihu-Shu-Gan-San (CSGS), a traditional Chinese medicine (TCM) formula containing seven herbal medicines, has been used in treatment of gastritis, peptic ulcer, irritable bowel syndrome and depression clinically. However, the chemical constituents in CSGS had not been studied so far. To quickly identify the chemical constituents of CSGS and to understand the chemical profiles related to antioxidant activity of CSGS, liquid chromatography coupled with electrospray ionization hybrid linear trap quadrupole orbitrap (LC-LTQ-Orbitrap) mass spectrometry has been applied for online identification of chemical constituents in complex system, meanwhile, antioxidant profile of CSGS was investigated by the fraction collecting and microplate reading system. As a result, 33 chemical constituents in CSGS were identified. Among them, 13 components could be detected both in positive and in negative ion modes, 20 constituents were determined only in positive ion mode and 2 components were only detected in negative ion mode. Meanwhile, the potential antioxidant profile of CSGS was also characterized by combination of 96-well plate collection of elutes from HPLC analysis and microplate spectrophotometer, in which the scavenging activities of free radical produced by DPPH of each fraction could be directly investigated by the analysis of microplate reader. This study quickly screened the contribution of CSGS fractions to the antioxidant activity and online identified the corresponding active constituents. The results indicated that the combination of LC-MS(n) and 96-well plate assay system established in this paper would be a useful strategy for correlating the chemical profile of TCMs with their bioactivities without isolation and purification.

Lactonecembranoids from Croton laevigatus.

Six new cembranoids, laevigatlactones A-F (1-6), and the known compound neocrotocembraneic acid (7) were isolated from leaves of Croton laevigatus. Their structures were elucidated on the basis of spectroscopic analysis, and that of 1 was confirmed by X-ray crystallography. Compound 2 exhibited modest cytotoxicity against HeLa cells, with an IC(50) value of 38.4 microM.

Flavonoids from the stems of Croton caudatus Geisel. var. tomentosus Hook.

A new flavone, named crotoncaudatin (1), was isolated from the stems of Croton caudatus Geisel. var. tomentosus Hook., together with nine known analogues: 3,5,6,7,8,3',4'-heptamethoxyflavone (2), tangeretin (3), nobiletin (4), 5,6,7,4'-tetramethoxy-flavone (5), sinensetin (6), kaempferol (7), tiliroside (8), kaempferol-3-O-rutinoside (9) and rutin (10). The structures of the above compounds were established by a combination of spectroscopic methods, including HR-ESI-MS, 1H-NMR, 13C-NMR, HMQC and HMBC spectra. All compounds were isolated from and identified in this species for the first time and compounds 1-6 are new for the genus Croton.