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Background: Vitiligo is a complex disorder characterized by skin depigmentation; the canonical Wnt signaling pathway that involves β -catenin plays a crucial role in promoting the melanin production in melanocytes. Targeted inhibition of the Janus kinase JAK-STAT pathway can effectively diminish the secretion of the chemokine C-X-C motif ligand CXCL10, thereby safeguarding melanocytes. Ferula has been applied as a treatment regimen for a long period; however, its use for the treatment of vitiligo has not been previously documented., Methods: CCK-8 assay, Intracellular melanin content assay, Tyrosinase activity assay, Western blotting, qRT-PCR, and ELISA methods were employed. Using molecular docking verified the inhibitory effects of feshurin on the JAK1., Results: The sesquiterpene coumarin feshurin was separated from Ferula samarcandica . Feshurin was shown to induce GSK-3 β phosphorylation, resulting in the translocation of β -catenin into the nucleus. This translocation subsequently upregulated the transcription of microphthalmia-associated transcription factor (MITF), leading to increased tyrosinase activity and melanin production. In addition, feshurin inhibited the production of chemokine CXCL10 via the JAK-STAT signaling pathway, which was verified by molecular docking., Conclusions: Based on these findings, it can be concluded that feshurin exhibits significant potential for the development of novel anti-vitiligo therapeutics.

Cardiovascular disease is the first cause of death worldwide and kills more people each year than any other cause of death. N, N-dimethylaniline-heliamine (DH), a synthetic tetrahydroisoquinoline alkaloid, has shown notable antiarrhythmic activity. However, the metabolic processes and pharmacokinetic characteristics of DH in rats have not been studied. This study aims to identify its metabolites, as well as develop and validate a rapid and efficient bioanalytical method for quantifying DH in rat plasma over a wide range of concentrations. Its metabolites were characterized in silico, in vitro, and in vivo. A series of 16 metabolites were identified, of which 12 were phase I metabolites and 4 were phase II metabolites. A low probability of DH binding to DNA, protein, and glutathione is predicted by the in silico model. The main metabolic processes of DH were demethylation, dehydrogenation, glucuronidation, and sulfation. Concentration-time profiles were generated by analyzing the plasma, and the outcomes were analyzed via non-compartmental analysis to identify the pharmacokinetic parameters. Among the detected parameters were the volume of distribution, estimated at 126,728.09 ± 56,867.09 mL/kg, clearance at 30,148.65 ± 15,354.27 mL/h/kg, and absolute oral bioavailability at 16.11%. The plasma distribution volume of DH was substantially higher than the overall plasma volume of rats, which suggests that DH has a specific tissue distribution in rats. This study suggests that DH is appropriately bioavailable and excreted via a variety of routes and has low toxicity.

Background and Aim: Agarikon pill (AGKP), a traditional Chinese herbal formula, and has been used for chronic obstructive pulmonary disease (COPD) treatment clinically. However, the active components and exact pharmacological mechanisms are still unclear. We aimed to investigate the therapeutic effects and mechanisms of AGKP on COPD and identify the chemical constituents and active compounds., Experimental Procedure: The chemical components of AGKP were identified by ultrahigh-performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). Network pharmacology analysis was performed to uncover the potential mechanism of AGKP. The efficiencies and mechanisms of AGKP were further confirmed in COPD animal models., Results and Conclusion: Ninety compounds from AGKP, such as flavonoids, triterpenoids, saponins, anthracenes, derivatives, phenyl propionic acid, and other organic acids, were identified in our study. AGKP improved lung function and pathological changes in COPD model rats. Additionally, inflammatory cell infiltration and proinflammatory cytokine levels were markedly reduced in COPD rats administered AGKP. Network pharmacology analysis showed that the inflammatory response is the crucial mechanism by which AGKP exerts therapeutic effects on COPD rats. WB and PCR data indicated that AGKP attenuated the inflammatory response in COPD model rats. AGKP reduces the pulmonary inflammatory response through the PI3K/AKT and MAPK TLR/NF-κB signaling pathways and exerts therapeutic effects via inhibition of inflammation and mucus hypersecretion on COPD model rats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Tetrahydroisoquinolines have been widely investigated for the treatment of arrhythmias. 1-(3'-bromophenyl)-heliamine (BH), an anti-arrhythmias agent, is a synthetic tetrahydroisoquinoline. This study focuses on the pharmacokinetic characterization of BH, as well as the identification of its metabolites, both in vitro and in vivo. A UHPLC-MS/MS method was developed and validated to quantify BH in rat plasma with a linear range of 1-1000 ng/mL. The validated method was applied to a pharmacokinetic study in rats. The maximum concentration C max (568.65 ± 122.14 ng/mL) reached 1.00 ± 0.45 h after oral administration. The main metabolic pathways appeared to be phase-I of demethylation, dehydrogenation, and epoxidation, and phase II of glucuronide and sulfate metabolites. Finally, a total of 18 metabolites were characterized, including 10 phase I metabolites and 8 phase II metabolites. Through the above studies, we have gained a better understanding of the absorption and metabolism of BH in vitro and in vivo, which will provide us with guidance for future in-depth studies on this compound.

Laetiporus sulphureus is a popular medicinal mushroom with diverse pharmacological activities in many Asian countries. Four new triterpenoids, named sulphurenoids A-D ( 1 - 4 ), along with 12 known analogues, were isolated from the fruits of L. sulphureus . Nuclear magnetic resonance, infrared spectroscopy, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) techniques were used for the investigation of the chemical structure of isolated compounds. In addition, the anti-inflammatory activity of three new compounds ( 2 - 4 ) was tested for NO production in lipopolysaccharide-induced RAW 264.7 cells. The IC 50 values of isolated triterpenoids ranged from 14.3 to 42.3 μM, which were more effective than the positive control (IC 50 for minocycline was 73.0 μM). The experimentally obtained anti-inflammatory activity data of L. sulphureus are in agreement with its traditional use., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Central Asia is the center of origin and diversification of the Artemisia genus. The genus Artemisia is known to possess a rich phytochemical diversity. Artemisinin is the shining example of a phytochemical isolated from Artemisia annua , which is widely used in the treatment of malaria. There is great interest in the discovery of alternative sources of artemisinin in other Artemisia species. Methods: The hexane extracts of Artemisia plants were prepared with ultrasound-assisted extraction procedures. Silica gel was used as an adsorbent for the purification of Artemisia annua extract. High-performance liquid chromatography with ultraviolet detection was performed for the quantification of underivatized artemisinin from hexane extracts of plants. Results: Artemisinin was found in seven Artemisia species collected from Tajikistan. Content of artemisinin ranged between 0.07% and 0.45% based on dry mass of Artemisia species samples. Conclusions: The artemisinin contents were observed in seven Artemisia species. A. vachanica was found to be a novel plant source of artemisinin. Purification of A. annua hexane extract using silica gel as adsorbent resulted in enrichment of artemisinin.

The new coumarin 1, yuganin A (7-methoxy-8-((1S,2S)-1,2,3-trihydroxy-3-methylbutyl)-2H-chromen-2-one) along with nine known coumarins, heraclenol 3'-O-β-D-glucopyranoside (2), oxypeucedanin hydrate 3'-O-β-D-glucopyranoside (3), heraclenol (4), oxypeucedanin hydrate (5), osthole (6), oxypeucedanin (7), heraclenin (8), isoimperatorin (9), imperatorin (10) and the disaccharide sucrose (11), have been isolated from the roots of Prangos pabularia, and the structures of these isolated compounds were elucidated by spectroscopic means, especially, UV, HR-ESIMS, and 1D and 2D NMR spectroscopy. Furthermore, the anti-melanogenic effect of yuganin A and its inhibitory effect on B16 cells were evaluated. Yuganin A may be useful in the treatment of hyperpigmentation and as a skin-whitening agent in the cosmetics industry.

As an active compound, psoralen is present in various Chinese herbal medicines and has exhibited significant activity in skin disease treatment. Its derivative 8-methoxypsoralan (8-MOP) is the most commonly used drug to induce repigmentation of vitiligo. In our previous screening assays, 4-methyl-6-phenyl-2H-furo[3,2-g]chromen-2-one (MPFC), a psoralen derivative, was identified as more effective tyrosinase and melanin activator than the positive control 8-MOP in consideration of low doses, as well as low toxicity. The overall purpose of this study was to characterize the melanogenic effect and mechanisms of MPFC in B16 cells. The melanin biosynthesis effects of MPFC were determined by examination of cellular melanin contents, tyrosinase activity assay, cyclic adenosinemonophosphate (cAMP) assay, and western blotting of MPFC-stimulated B16 mouse melanoma cells. Our results showed that MPFC enhanced both melanin synthesis and tyrosinase activity in a concentration-dependent manner as well as significantly activated the expression of melanogenic proteins such as tyrosinase, tyrosinase-related protein-1 and tyrosinase-related protein-2. Western blot analysis showed that MPFC increased the phosphorylation of p38 mitogen-activated protein kinase and cAMP response element-binding protein (CREB) as well as the expression of microphthalmia-associated transcription factor (MITF). Moreover, MPFC stimulated intracellular cAMP levels and induced tyrosinase activity and melanin synthesis were attenuated by H89, a protein kinase A inhibitor. These results indicated that MPFC-mediated activation of the p38 MAPK and the protein kinase A (PKA) pathway may shed light on a novel approach for an effective therapy for vitiligo.

Plants or plant-derived products have been routinely used in several traditional medicine systems for vitiligo treatment. It is well-known that melanogenesis can be promoted by certain flavonoid compounds isolated from the traditional Uyghur medicinal plant, Kaliziri. Therefore, Chalcones, one class of flavonoid compounds, has become an interesting target for the development of anti-vitiligo agents. A series of novel isoxazole chalcone derivatives have been designed, synthesized, and evaluated for biological activities by our group. Among them, derivative 1-(4-((3-phenylisoxazol-5-yl)methoxy)phenyl)-3-phenylprop-2-en-1-one (PMPP) was identified as a potent tyrosinase activator with better activity and lower toxicity than the positive control 8-methoxypsoralen (8-MOP) in this study. Further investigations revealed that Akt and GSK3β were the signaling pathways involved in the hyperpigmentation of PMPP. Overall, these studies may provide a convenient and novel approach for the further development of anti-vitiligo agents., Competing Interests: All authors declare that there are no conflict of interest.

The root of Geranium collinum Steph is known in Tajik traditional medicine for its hepatoprotective, antioxidant, and anti-inflammatory therapeutic effects. The present study was conducted to evaluate of potential antidiabetic, antioxidant activities, total polyphenolic and flavonoid content from the different extracts (aqueous, aqueous-ethanolic) and individual compounds isolated of the root parts of G. collinum . The 50% aqueous-ethanolic extract possesses potent antidiabetic activity, with IC 50 values of 0.10 μg/mL and 0.09 μg/mL for the enzymes protein-tyrosine phosphatase (1B PTP-1B) and α-glucosidase, respectively. Phytochemical investigations of the 50% aqueous-ethanolic extract of G. collinum , led to the isolation of ten pure compounds identified as 3,3',4,4'-tetra- O -methylellagic acid ( 1 ), 3,3'-di- O -methylellagic acid ( 2 ), quercetin ( 3 ), caffeic acid ( 4 ), (+)-catechin ( 5 ), (-)-epicatechin ( 6 ), (-)-epigallocatechin ( 7 ), gallic acid ( 8 ), β-sitosterol-3- O -β-d-glucopyranoside ( 9 ), and corilagin ( 10 ). Their structures were determined based on 1D and 2D NMR and mass spectrometric analyses. Three isolated compounds exhibited strong inhibitory activity against PTP-1B, with IC 50 values below 0.9 μg/mL, more effective than the positive control (1.46 μg/mL). Molecular docking analysis suggests polyphenolic compounds such as corilagin, catechin and caffeic acid inhibit PTP-1B and β-sitosterol-3- O -β-d-gluco-pyranoside inhibits α-glucosidase. The experimental results suggest that the biological activity of G. collinum is related to its polyphenol contents. The results are also in agreement with computational investigations. Furthermore, the potent antidiabetic activity of the 50% aqueous-ethanolic extract from G. collinum shows promise for its future application in medicine. To the best of our knowledge, we hereby report, for the first time, the antidiabetic activity of G. collinum., Competing Interests: The authors confirm that there are no conflicts of interest associated with this publication.

Rupestonic acid, a potential anti-influenza agent, is an important and characteristic compound in Artemisia rupestris L., a well-known traditional Uighur medicine for the treatment of colds. In the present study, high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry was used to detect and identify the metabolites in rat urine after oral administration of rupestonic acid. A total of 10 metabolites were identified or partially characterized. The structure elucidations of the metabolites were performed by comparing the changes in accurate molecular masses and fragment ions with those of the parent compound. The results showed that the main metabolites of rupestonic acid in rat urine were formed by oxidation, hydrogenation and glucuronidation. A metabolism pathway was proposed for the first time based on the characterized structures. This metabolism study can provide essential information for drug discovery, design and clinical application of rupestonic acid., (Copyright © 2014 John Wiley & Sons, Ltd.)

Isoflavones are important chemical components of the seeds and sprouts of chickpeas. We systematically investigated the effects of isoflavones extracted from chickpea sprouts (ICS) on the human breast cancer cell lines SKBr3 and Michigan Cancer Foundation-7 (MCF-7). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that ICS (10-60 µg/mL) significantly inhibited the proliferation of both cell lines in a time-dependent and dose-dependent fashion. Wright-Giemsa staining as well as annexin V-fluorescein isothiocyanate and propidium iodide (Annexin V/PI) staining showed that ICS significantly increased cytoclasis and apoptotic body formation. Quantitative Annexin V/PI assays further showed that the number of apoptotic cells increased in a dose-dependent manner following ICS treatment. Semiquantitative reverse transcription PCR showed that ICS increased the expression of the apoptosis-promoting gene Bcl-2-associated X protein and decreased the expression of the antiapoptotic gene Bcl-2. Western blot analysis showed that treatment of SKBr3 and MCF-7 cells with ICS increased the expression of caspase 7, caspase 9, P53, and P21 in a dose-dependent manner. Flow cytometry assays using the fluorescent probe 3,3'-dihexyloxacarbocyanine iodide showed a dose-dependent decrease in mitochondrial membrane potential following ICS treatment. Treatment using ICS also induced a dose-dependent increase in reactive oxygen species production. This is the first study to demonstrate that ICS may be a chemopreventive or therapeutic agent against breast cancer., (Copyright © 2014 John Wiley & Sons, Ltd.)

Chlorogenic acid (CGA), the ester formed between caffeic acid and l-quinic acid, is a widespread phenolic compound. It is part of the human diet, found in foods such as coffee, apples, pears, etc. CGA is also was widely used in cosmetics, but the effects of CGA on melanogenesis are unknown. In this study, we analyzed the effects of CGA on cell proliferation, melanin content and tyrosinase of B16 murine melanoma cells. Additionally, the enzymatic reactions of CGA in B16 melanoma cells lytic solution were detected by UV spectrophotometry. Results showed CGA at 30 and 60 μM significantly suppresses cell proliferation. 8-MOP at 100 μM significantly promotes cell proliferation, but CGA can counter this. Incubated for 24 h, CGA (500 μM) improves melanogenesis while suppressing tyrosinase activity in B16 melanoma cells or 8-methoxypsoralen (8-MOP) co-incubated B16 melanoma cells. After 12 h, B16 melanoma cell treatment with CGA leads to an increase in melanin accumulation, however, after 48 h there is a decrease in melanin production which correlates broadly with a decrease in tyrosinase activity. CGA incubated with lytic solution 24 h turned brown at 37 °C. The formation of new products (with a maximum absorption at 295 nm) is associated with reduction of CGA (maximum absorption at 326 nm). Therefore, CGA has its two sidesroles in melanogenesis of B16 melanoma cells. CGA is a likely a substrate of melanin, but the metabolic product(s) of CGA may suppress melanogenesis in B16 melanoma cells by inhibiting tyrosinase activity.