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Biomedical Chromatography : BMC May 2024Cnidii Fructus, derived from the dried ripe fruit of Cnidium monnieri (L.) Cuss, has the effect of warming kidneys and invigorating Yang. This study established the...
Cnidii Fructus, derived from the dried ripe fruit of Cnidium monnieri (L.) Cuss, has the effect of warming kidneys and invigorating Yang. This study established the spectrum-effect relationships between ultra-high-performance liquid chromatography (UHPLC) fingerprints and the antitumor activities of Cnidii Fructus on human hepatocellular carcinoma (HepG2) cells. In UHPLC fingerprints, 19 common peaks were obtained, and 17 batches of herbs had similarity >0.948. In Cell Counting Kit-8 (CCK-8) test, 17 batches of Cnidii Fructus extract significantly inhibited the proliferation of HepG2 cells to different degrees, showing different half-maximal inhibitory concentration (IC) values. Furthermore, gray correlation analysis, Pearson's analysis, and orthogonal partial least squares discriminant analysis were performed to screen out eight components. The analysis of mass spectrum data and a comparison with standards revealed that the eight components were methoxsalen, isopimpinellin, osthenol, imperatorin, osthole, ricinoleic acid, linoleic acid, and oleic acid. The verification experiments by testing single compounds indicated that these eight compounds were the major anti-hepatoma compounds in Cnidii Fructus. This work provides a model combining UHPLC fingerprints and antitumor activities to study the spectrum-effect relationships of Cnidii Fructus, which can be used to determine the principal components responsible for the bioactivity.
Topics: Chromatography, High Pressure Liquid; Humans; Hep G2 Cells; Cell Proliferation; Cnidium; Fruit; Drugs, Chinese Herbal; Liver Neoplasms; Carcinoma, Hepatocellular; Plant Extracts; Reproducibility of Results; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Furocoumarins
PubMed: 38368628
DOI: 10.1002/bmc.5847 -
Phytotherapy Research : PTR Apr 2024Macrophage inflammation plays a central role during the development and progression of sepsis, while the regulation of macrophages by parthanatos has been recently...
Macrophage inflammation plays a central role during the development and progression of sepsis, while the regulation of macrophages by parthanatos has been recently identified as a novel strategy for anti-inflammatory therapies. This study was designed to investigate the therapeutic potential and mechanism of pimpinellin against LPS-induced sepsis. PARP1 and PAR activation were detected by western blot or immunohistochemistry. Cell death was assessed by flow cytometry and western blot. Cell metabolism was measured with a Seahorse XFe24 extracellular flux analyzer. C57, PARP1 knockout, and PARP1 conditional knock-in mice were used in a model of sepsis caused by LPS to assess the effect of pimpinellin. Here, we found that pimpinellin can specifically inhibit LPS-induced macrophage PARP1 and PAR activation. In vitro studies showed that pimpinellin could inhibit the expression of inflammatory cytokines and signal pathway activation in macrophages by inhibiting overexpression of PARP1. In addition, pimpinellin increased the survival rate of LPS-treated mice, thereby preventing LPS-induced sepsis. Further research confirmed that LPS-induced sepsis in PARP1 overexpressing mice was attenuated by pimpinellin, and PARP1 knockdown abolished the protective effect of pimpinellin against LPS-induced sepsis. Further study found that pimpinellin can promote ubiquitin-mediated degradation of PARP1 through RNF146. This is the first study to demonstrate that pimpinellin inhibits excessive inflammatory responses by promoting the ubiquitin-mediated degradation of PARP1.
Topics: Animals; Mice; Inflammation; Lipopolysaccharides; Macrophages; Methoxsalen; Mice, Inbred C57BL; Sepsis; Ubiquitination; Ubiquitins
PubMed: 38323338
DOI: 10.1002/ptr.8135 -
Scientific Reports Jan 2024We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for... (Meta-Analysis)
Meta-Analysis
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Topics: Humans; Etoposide; Methoxsalen; Azathioprine; Melphalan; Busulfan; Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Cyclosporins; Pharmaceutical Preparations
PubMed: 38172159
DOI: 10.1038/s41598-023-50602-6 -
Journal of the Formosan Medical... Dec 2023Vitiligo is a common acquired disease of pigment loss. In lesions recalcitrant to non-invasive treatment, transplantation of cultured autologous melanocytes is an...
Vitiligo is a common acquired disease of pigment loss. In lesions recalcitrant to non-invasive treatment, transplantation of cultured autologous melanocytes is an emerging choice. Conventionally, the recipient site is often prepared by laser-mediated or mechanical dermabrasion. Such preparation procedures have disadvantages including prolonged transplantation duration, long period for reepithelialization and potential scarring. We propose a method of preparing recipient sites by psoralen and controlled ultraviolet A (PUVA)-induced blistering followed by transplanting suspended melanocytes. We introduced this method in 10 patients with segmental vitiligo on their recipient site 3 to 5 days before transplantation and blistering developed in 2 to 3 days afterwards. On the day of transplantation, the blister roof could be peeled off easily without bleeding and the recipient site preparation could be completed in 20 min. The recipient site became reepithelialized within 1 week. Progressive repigmentation was observed for up to 6 months, with an average of 65.06% repigmentation in the recipient site without scarring at the end of follow-up. Hence, preparation of the recipient site by controlled PUVA-induced sunburn-like blistering can potentially facilitate melanocyte transplantation and prevent scarring.
PubMed: 38158260
DOI: 10.1016/j.jfma.2023.12.005 -
Cureus Nov 2023Skin of color refers to individuals whose skin color ranges from very light beige to very dark brown. Anthropologists and sociologists have previously recognized the...
Colorimetric Scale for Skin of Color: A Practical Classification Scale for the Clinical Assessment, Dermatology Management, and Forensic Evaluation of Individuals With Skin of Color.
Skin of color refers to individuals whose skin color ranges from very light beige to very dark brown. Anthropologists and sociologists have previously recognized the importance of an objective classification of skin color for individuals with skin of color that does not include race and ethnicity. Since 1975, dermatologists have used the Fitzpatrick classification of sun-reactive skin types to categorize patients with skin of color; this classification was established for psoriasis patients participating in using oral methoxsalen and phototherapy clinical trial to determine the initial ultraviolet A dose. The Fitzpatrick classification merely classifies individuals as white, brown, and black; the individuals with white skin are further divided into four groups based on their burning or tanning capacity. This classification system does not provide reliable information with regard to the risk of skin cancer for individuals with darker skin color and does not aid in the evaluation of medical conditions with cutaneous involvement or assessment of appropriate cosmetic interventions for aesthetic management. Many clinicians, including forensic pathologists, incorporate the patient's race or ethnicity in their medical evaluation to describe the individual's skin color. Established scales for skin of color either include white skin color, or include 10 or more color types, or include both. We introduce a simple and rapidly performed scale that is not based on race or ethnicity to categorize persons with skin of color. The colorimetric scale ranges from very light beige to very dark brown and does not include white skin. The scale has five colors ranging from lightest (skin color type 1) to darkest (skin color type 5): very light beige (skin color type 1), light brown (skin color type 2), medium brown (skin color type 3), dark brown (skin color type 4), and very dark brown (skin color type 5); an individual with white skin would have a skin color type 0 in this classification of patient skin color. In conclusion, a scale that is not based on race or ethnicity is useful for categorizing individuals with skin of color not only for sociologists but also for clinicians who treat these patients. This colorimetric scale will be helpful for dermatologists to categorize persons with skin of color to predict their risk for developing skin cancer and to assessing appropriate cosmetic procedures and devices for these patients. In addition, the colorimetric scale will be useful for not only forensic pathologists but also other clinicians to provide a non-racial and non-ethnic designation of skin color type for their patients.
PubMed: 38046737
DOI: 10.7759/cureus.48132 -
Heliyon Nov 2023Vitiligo stands as a challenging skin disorder with limited treatment options available. LiuWei DiHuang formula (LDF), a renowned Traditional Chinese medicine, has...
BACKGROUND
Vitiligo stands as a challenging skin disorder with limited treatment options available. LiuWei DiHuang formula (LDF), a renowned Traditional Chinese medicine, has exhibited promising results in treating vitiligo over an extended period. However, the precise underlying mechanism of its action remains elusive.
METHODS
Employing a comprehensive network pharmacology approach, this study identified active compounds and their corresponding targets within LDF, while also pinpointing vitiligo-associated targets sourced from the TCMSP database, OMIM, DisGenNET, and Genecards. A network was established to illustrate the connections between active compounds and targets, alongside a protein-protein interaction network. Further analyses, encompassing Gene Ontology (GO) function and KEGG pathway enrichment, were conducted using the DAVID platform. Molecular docking simulations were performed utilizing AutoDockTools and AutoDockVina software. To validate the outcomes of the systematic pharmacological investigation, experiments were conducted using juvenile zebrafish.
RESULTS
The collective effort of the network pharmacology approach yielded a compilation of 41 compounds and 192 targets. Molecular docking simulations notably revealed the lowest binding energies for CAT-quercetin and CAT-Kaempferol interactions. The utilization of juvenile zebrafish experiments highlighted a significant increase in melanocyte count following methoxsalen and LDF treatment. Notably, LDF prominently augmented the expression levels of proteins related to melanogenesis. Additionally, LDF showcased the capacity to enhance CAT and SOD levels while concurrently reducing ROS and MDA activity. In contrast to the model group, substantial increases in protein and mRNA levels of Nrf2 and HO-1 were observed in response to LDF treatment (P < 0.05).
CONCLUSION
Through a meticulous network pharmacology approach, this study successfully predicted active components and potential targets associated with LDF's application in vitiligo treatment. The therapeutic effectiveness of LDF against vitiligo is postulated to stem from its regulation of oxidative stress factors and the Nrf2/HO-1 pathway.
PubMed: 38027573
DOI: 10.1016/j.heliyon.2023.e21744 -
Pesticide Biochemistry and Physiology Nov 2023Spodoptera litura, a polyphagous lepidopteran pest, demonstrates a remarkable capacity to adapt to varying host plants by efficiently detoxifying phytochemicals....
Spodoptera litura, a polyphagous lepidopteran pest, demonstrates a remarkable capacity to adapt to varying host plants by efficiently detoxifying phytochemicals. However, the underlying mechanism for this adaptation is not well understood. Herein, twenty eplison glutathione S-transferase genes (GSTes) were characterized and their roles in phytochemical tolerance were analyzed in S. litura. Most of the GSTe genes were mainly expressed in the larval midgut and fat body. Exposure to the phytochemicals, especially xanthotoxin, induced the expression of most GSTe genes. Molecular docking analysis revealed that xanthotoxin could form stable bonds with six xanthotoxin-responsive GSTes, with binding free energies ranging from -36.44 to -68.83 kcal mol. Knockdown of these six GSTe genes increased the larval susceptibility to xanthotoxin. Furthermore, xanthotoxin exposure significantly upregulated the expression of two transcription factor genes CncC and MafK. Silencing of either CncC or MafK reduced the expression of GSTe16, which exhibited the largest change in response to xanthotoxin. Additionally, analysis of the promoter sequence of GSTe16 revealed the presence of seven CncC/Maf binding sites. Luciferase reporter assays showed that CncC and MafK enhanced the expression of GSTe16, leading to the increased xanthotoxin tolerance in S. litura. These findings provide insight into the functions and transcriptional regulatory mechanisms of GSTes, thereby enhancing our understanding of the role of GSTs in the adaptation of lepidopteran pests to phytochemicals.
Topics: Animals; Spodoptera; Methoxsalen; Molecular Docking Simulation; Glutathione; Transferases; Larva; Insecticides
PubMed: 37945225
DOI: 10.1016/j.pestbp.2023.105592 -
Journal of Dermatological Science Dec 2023
Topics: Ficusin; Proteomics; Skin; Ultraviolet Therapy; PUVA Therapy; Methoxsalen
PubMed: 37914600
DOI: 10.1016/j.jdermsci.2023.09.004 -
Biochemical and Biophysical Research... Dec 2023Epidemiological studies have found that high citrus fruit consumption was associated with higher risk of skin cancer. Citrus fruits and some vegetables contain...
Epidemiological studies have found that high citrus fruit consumption was associated with higher risk of skin cancer. Citrus fruits and some vegetables contain furocoumarins, which may interact with ultraviolet radiation to induce skin cancer. We aimed to determine the effects of two furocoumarins, including 8-methoxypsoralen (8-MOP) and 6',7'-dihydroxybergamottin (DHB), on UVA-induced DNA damage in human epidermal melanocytes, the origin of melanoma. Our hypothesis was that these dietary furocoumarins increase UVA-induced DNA damage in melanocytes, compared to cells exposed to UV alone. We incubated melanocytes with 8-MOP or DHB, followed by exposure to physiological doses of UVA radiation. We used Western blots to quantify the UVA-induced DNA damage measured by the fraction of phosphorylated histone variant H2AX (γH2AX), which is a marker of DNA damage, relative to total H2AX (γH2AX/H2AX) in the presence or absence of furocoumarins. To quantify the UVA-induced change in γH2AX/H2AX, we calculated the UVA:Control ratio as the ratio of γH2AX/H2AX in UVA-exposed cells to that in cells without UVA (control). The mean UVA:Control ratios were borderline significantly higher for cells treated with 8-MOP and significantly higher for cells treated with DHB, compared to that of untreated cells. This study suggests that furocoumarins (particularly 8-MOP and DHB) enhance UVA-induced DNA damage in melanocytes, which is a potential novel mechanism for citrus and furocoumarins to elevate the risk of skin cancer.
Topics: Humans; Furocoumarins; Methoxsalen; Ultraviolet Rays; Melanocytes; DNA Damage; Skin Neoplasms; Citrus
PubMed: 37866241
DOI: 10.1016/j.bbrc.2023.09.094 -
The European Journal of Neuroscience Oct 2023Xanthotoxin (XAT) is a natural furanocoumarin clinically used in the treatment of skin diseases such as vitiligo and psoriasis. Recent studies have also investigated its...
Xanthotoxin (XAT) is a natural furanocoumarin clinically used in the treatment of skin diseases such as vitiligo and psoriasis. Recent studies have also investigated its effects on anti-inflammatory, anti-cognitive dysfunction, and anti-amnesia as a guideline for clinic application. However, little is known about its effects on pain relief. Here, we tested the analgesic effects of XAT in serious acute pain and chronic pain models. For acute pain, we used hot-, capsaicin- and formalin-induced paw licking. Nociceptive threshold was measured by mechanical stimuli with von Frey filaments. For chronic pain, we injected complete Freund's adjuvant (CFA) into the mice's plantar surface of the hind paw to induce inflammatory pain. Heat and mechanical hyperalgesia were evaluated by radiant heat and von Frey filament tests, respectively. To investigate the mechanisms underlying the analgesic effect of XAT, we used calcium imaging and western blot to assess transient receptor potential vanilloid 1 (TRPV1) activity and expression in isolated L4-L6 dorsal root ganglion (DRG) neurons. Haematoxylin and eosin (HE) staining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to examine immune cell recruitment and proinflammatory factor release from skin tissue from paw injection sites. Our results demonstrated that XAT not only reduced acute pain behaviors generated by hot, capsaicin, and formalin but also attenuated CFA-induced heat and mechanical hyperalgesia. The analgesic activity of XAT may be achieved by controlling peripheral inflammation, lowering immune cell infiltration at the site of inflammatory tissue, reducing inflammatory factor production, and therefore inhibiting TRPV1 channel sensitization and expression.
Topics: Mice; Animals; Hyperalgesia; Chronic Pain; Methoxsalen; Capsaicin; Acute Pain; Analgesics; Anti-Inflammatory Agents; Inflammation; Formaldehyde; Ganglia, Spinal
PubMed: 37671643
DOI: 10.1111/ejn.16119