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Pharmaceuticals (Basel, Switzerland) Jun 2024Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic...
Neuropathic pain (NP) is a common type of chronic pain caused by a lesion or disease of the somatosensory nervous system. This condition imposes a considerable economic burden on society and patients. Daphnetin (DAP) is a natural product isolated from a Chinese medicinal herb with various pharmacological activities, such as anti-inflammatory and analgesic properties. However, the underlying mechanisms of these effects are not fully understood. In the present study, we aimed to investigate DAP's anti-inflammatory and analgesic effects and explore the underlying mechanisms of action. The NP model was established as chronic constrictive injury (CCI) of the sciatic nerve, and pain sensitivity was evaluated by measuring the mechanical withdrawal threshold (MWT) and thermal withdrawal threshold (TWT). The activation of microglia in the spinal dorsal horn was measured via immunofluorescence staining. Protein levels were measured using a western blot assay. Using a mass-spectrometry proteomics platform and an LC-MS/MS-based metabolomics platform, proteins and metabolites in spinal cord tissues were extracted and analyzed. DAP treatment ameliorated the MWT and TWT in CCI rats. The expression of IL-1β, IL-6, and TNF-α was inhibited by DAP treatment in the spinal cords of CCI rats. Moreover, the activation of microglia was suppressed after DAP treatment. The elevation in the levels of P2X, IRF8, IRF5, BDNF, and p-P38/P38 in the spinal cord caused by CCI was inhibited by DAP. Proteomics and metabolomics results indicated that DAP ameliorated the imbalance of glycerophospholipid metabolism in the spinal cords of CCI rats. DAP can potentially ameliorate NP by regulating microglial responses and glycerophospholipid metabolism in the CCI model. This study provides a pharmacological justification for using DAP in the management of NP.
PubMed: 38931456
DOI: 10.3390/ph17060789 -
Pharmaceuticals (Basel, Switzerland) Jun 2024TRPV1 channels are polymodal cation channels located predominantly on primary afferent neurons that are activated by inflammatory mediators, capsaicin (the active... (Review)
Review
TRPV1 channels are polymodal cation channels located predominantly on primary afferent neurons that are activated by inflammatory mediators, capsaicin (the active component in chili peppers), and noxious heat. TRPV1 channel antagonists are potential new analgesic agents, but their development has been hindered by the finding that they also produce loss of thermal homeostasis and response to noxious heat. Results from recent studies of the TRPV1 channel indicate that it might be possible to develop TRPV1 channel antagonists that inhibit pain without affecting noxious heat sensation. TRPV1 channels are also present in the central nervous system (CNS) and have been implicated in learning, memory, and behaviour. TRPV1 channel modulators have been proposed to have possible therapeutic potential in the treatment of neurological and psychiatric conditions. However, further understanding of the role of TRPV1 channels in the CNS is required before therapeutic advances in the treatment of neuropsychiatric conditions with TRPV1 channel modulators can be made.
PubMed: 38931423
DOI: 10.3390/ph17060756 -
Nutrients Jun 2024The excessive employment of acetaminophen (APAP) is capable of generating oxidative stress and apoptosis, which ultimately result in acute liver injury (ALI)....
The excessive employment of acetaminophen (APAP) is capable of generating oxidative stress and apoptosis, which ultimately result in acute liver injury (ALI). polysaccharides (GLPs) exhibit hepatoprotective activity, yet the protective impact and potential mechanism of GLPs in relation to APAP-induced ALI remain ambiguous. The intention of this research was to scrutinize the effect of GLPs on APAP-induced ALI and to shed light on their potential mechanism. The results demonstrated that GLPs were capable of notably alleviating the oxidative stress triggered by APAP, as shown through a significant drop in the liver index, the activities of serum ALT and AST, and the amounts of ROS and MDA in liver tissue, along with an increase in the levels of SOD, GSH, and GSH-Px. Within these, the hepatoprotective activity at the high dose was the most conspicuous, and its therapeutic efficacy surpassed that of the positive drug (bifendate). The results of histopathological staining (HE) and apoptosis staining (TUNEL) indicated that GLPs could remarkably inhibit the necrosis of hepatocytes, the permeation of inflammatory cells, and the occurrence of apoptosis induced by APAP. Moreover, Western blot analysis manifested that GLPs enhanced the manifestation of Nrf2 and its subsequent HO-1, GCLC, and NQO1 proteins within the Nrf2 pathway. The results of qPCR also indicated that GLPs augmented the expression of antioxidant genes Nrf2, HO-1, GCLC, and NQO1. The results reveal that GLPs are able to set off the Nrf2 signaling path and attenuate ALI-related oxidative stress and apoptosis, which is a potential natural medicine for the therapy of APAP-induced liver injury.
Topics: Acetaminophen; Oxidative Stress; Apoptosis; Reishi; Chemical and Drug Induced Liver Injury; NF-E2-Related Factor 2; Animals; Male; Polysaccharides; Signal Transduction; Liver; Mice; Fungal Polysaccharides; Antioxidants
PubMed: 38931214
DOI: 10.3390/nu16121859 -
Nutrients Jun 2024Saikosaponin D (SSD), derived from L., has various pharmacological properties, including immunoregulatory, anti-inflammatory, and anti-allergic effects. Several studies...
Saikosaponin D (SSD), derived from L., has various pharmacological properties, including immunoregulatory, anti-inflammatory, and anti-allergic effects. Several studies have investigated the anti-tumor effects of SSD on cancer in multiple organs. However, its role in colorectal cancer (CRC) remains unclear. Therefore, this study aimed to elucidate the suppressive effects of SSD on CRC cell survival and metastasis. SSD reduced the survival and colony formation ability of CRC cells. SSD-induced autophagy and apoptosis in CRC cells were measured using flow cytometry. SSD treatment increased LC3B and p62 autophagic factor levels in CRC cells. Moreover, SSD-induced apoptosis occurred through the cleavage of caspase-9, caspase-3, and PARP, along with the downregulation of the Bcl-2 family. In the in vivo experiment, a reduction in the number of metastatic tumor nodules in the lungs was observed after the oral administration of SSD. Based on these results, SSD inhibits the metastasis of CRC cells to the lungs by inducing autophagy and apoptosis. In conclusion, SSD suppressed the proliferation and metastasis of CRC cells, suggesting its potential as a novel substance for the metastatic CRC treatment.
Topics: Saponins; Oleanolic Acid; Autophagy; Colorectal Neoplasms; Apoptosis; Humans; Lung Neoplasms; Animals; Cell Line, Tumor; Cell Proliferation; Mice; Mice, Inbred BALB C; Antineoplastic Agents, Phytogenic; Xenograft Model Antitumor Assays; Cell Survival; Mice, Nude
PubMed: 38931199
DOI: 10.3390/nu16121844 -
Plants (Basel, Switzerland) Jun 2024is a traditional Chinese herbal medicine that grows in the Qinghai-Tibet Plateau region at a 3100-5000 m altitude. Iridoid compounds are the main active compounds of...
is a traditional Chinese herbal medicine that grows in the Qinghai-Tibet Plateau region at a 3100-5000 m altitude. Iridoid compounds are the main active compounds of the used as medical ingredients and display anti-inflammatory, analgesic, and hepatoprotective properties. To better understand the biological mechanisms of iridoid compounds in this species, we performed a comprehensive analysis of the transcriptome and metabolome of leaves from four different regions (3540-4270 m). Global metabolome profiling detected 575 metabolites, and 455 differentially accumulated metabolites (DAMs) were detected in leaves from the four regions. Eight major DAMs related to iridoid metabolism in leaves were investigated: shanzhiside methyl ester, 8-epideoxyloganic acid, barlerin, shanzhiside, geniposide, agnuside, feretoside, and catalpin. In addition, five soil physical and chemical indicators in rhizosphere soils were analyzed. Four significant positive correlations were observed between alkaline nitrogen and geniposide, exchangeable calcium and geniposide, available potassium and shanzhiside, and available phosphorus and shanzhiside methyl ester. The transcriptome data showed 12 cDNA libraries with 74.46 Gb of clean data, which formed 29,833 unigenes. Moreover, 78.91% of the unigenes were annotated using the eight public databases. Forty-one candidate genes representing 23 enzymes involved in the biosynthesis of iridoid compounds were identified in leaves. Moreover, the , , , and genes associated with iridoid biosynthesis were specifically expressed in . The integration of transcriptome and metabolome analyses highlights the crucial role of soil physical and chemical indicators and major gene expression related to iridoid metabolism pathways in from different areas. Our findings provide a theoretical foundation for exploring the molecular mechanisms underlying iridoid compound accumulation in .
PubMed: 38931059
DOI: 10.3390/plants13121627 -
Molecules (Basel, Switzerland) Jun 2024Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problem. Numerous studies have indicated that bioactive... (Review)
Review
Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problem. Numerous studies have indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, and has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, antihyperglycemic, anti-apoptotic, and antihyperlipidemic, among other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.
Topics: Curcumin; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Animals; Antioxidants; Anti-Inflammatory Agents
PubMed: 38930998
DOI: 10.3390/molecules29122934 -
Molecules (Basel, Switzerland) Jun 2024This review collects the synthetic modifications performed on andrographolide, a natural molecule derived from , for oncology applications. Various pharmacomodulations... (Review)
Review
This review collects the synthetic modifications performed on andrographolide, a natural molecule derived from , for oncology applications. Various pharmacomodulations were carried out, and the products were tested on different cancer cell lines. The impact of these modifications was analyzed with the aim of mapping the positions essential for activity to facilitate future research in this field. However, this study makes it clear that, in addition to structural modifications of the molecule, which can result in varying degrees of effectiveness in targeting interactions, the lipophilic capacity of the structures obtained through hemisynthesis is of significant importance.
Topics: Diterpenes; Humans; Antineoplastic Agents; Structure-Activity Relationship; Neoplasms; Andrographis; Cell Line, Tumor; Molecular Structure; Animals
PubMed: 38930949
DOI: 10.3390/molecules29122884 -
Molecules (Basel, Switzerland) Jun 2024Turmeric () contains curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Nevertheless, curcumin is the most researched active ingredient for its numerous...
Turmeric () contains curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). Nevertheless, curcumin is the most researched active ingredient for its numerous pharmacological effects. We investigated the impact of these curcuminoids found in Ryudai gold, an approved cultivar of , on wound healing, inflammation, and diabetes. Sub-planter injections of carrageenan induced acute paw inflammation in rats. The wound-healing ability of 1% curcuminoids was examined by making a 6 mm round wound on the shaved dorsum of the mice with a biopsy punch. A single intraperitoneal injection of streptozotocin (50 mg/kg) was used to induce diabetes in mice. Curcuminoids at a dose rate of 100 mg/kg body weight were used with feed and as a gastric gavage to treat diabetes and inflammation in experimental animals. Paw thickness was measured at 1, 3, and 6 h following carrageenan injection. After three hours, mean paw volume was 58% in carrageenan-injected mice, which was 35%, 37%, and 31% in the curcumin, DMC, and BDMC groups, respectively. Histopathology of the paw tissue demonstrated severe infiltration of inflammatory cells and thickening of the dermis, which were remarkably improved by the curcuminoids. The wound-healing abilities were significantly higher in the curcumin- (95.0%), DMC- (93.17%), and BDMC-treated (89.0%) groups, in comparison to that of the control (65.09%) group at day nine. There were no significant differences in wound-healing activity among the groups treated with 1% curcuminoids throughout the study. Streptozotocin-induced diabetes was characterized by an increased blood glucose (552.2 mg/dL) and decreased body weight (31.2 g), compared to that of the control rats (145.6 mg/dL and 46.8 g blood glucose and body weight, respectively). It also caused an increase in serum alanine aminotransferase (ALT; 44.2 U/L) and aspartate aminotransferase (AST; 55.8 U/L) compared to that of the control group (18.6 U/L and 20.1 U/L, respectively). Histopathological examination of the liver showed that diabetes caused hepatic cellular necrosis, congestion of the central vein, and parenchymatous degeneration. However, all three curcuminoids significantly decreased blood glucose levels, ALT, and AST and improved the histopathological score of the liver. These results evidenced that not only curcumin but also DMC and BDMC have potent anti-inflammatory, wound healing, and anti-diabetic efficacy, and the Ryudai gold variety of turmeric could be used as a functional food supplement.
Topics: Animals; Curcuma; Wound Healing; Mice; Rats; Diabetes Mellitus, Experimental; Anti-Inflammatory Agents; Hypoglycemic Agents; Curcumin; Male; Plant Extracts; Carrageenan; Inflammation; Diarylheptanoids
PubMed: 38930859
DOI: 10.3390/molecules29122795 -
Molecules (Basel, Switzerland) Jun 2024An RP-HPLC method with a UV detector was developed for the simultaneous quantification of diclofenac diethylamine, methyl salicylate, and capsaicin in a pharmaceutical...
An RP-HPLC method with a UV detector was developed for the simultaneous quantification of diclofenac diethylamine, methyl salicylate, and capsaicin in a pharmaceutical formulation and rabbit skin samples. The separation was achieved using a Thermo Scientific ACCLAIM 120 C column (Waltham, MA, USA, 4.6 mm × 150 mm, 5 µm). The optimized elution phase consisted of deionized water adjusted to pH = 3 using phosphoric acid mixed with acetonitrile in a 35:65% (/) ratio with isocratic elution. The flow rate was set at 0.7 mL/min, and the detection was performed at 205 nm and 25 °C. The method exhibits good linearity for capsaicin (0.05-70.0 µg/mL), methyl salicylate (0.05-100.0 µg/mL), and diclofenac diethylamine (0.05-100.0 µg/mL), with low LOD values (0.0249, 0.0271, and 0.0038 for capsaicin, methyl salicylate, and diclofenac diethylamine, respectively). The RSD% values were below 3.0%, indicating good precision. The overall greenness score of the method was 0.61, reflecting its environmentally friendly nature. The developed RP-HPLC method was successfully applied to analyze Omni Hot Gel pharmaceutical formulation and rabbit skin permeation samples.
Topics: Capsaicin; Diclofenac; Chromatography, High Pressure Liquid; Salicylates; Skin; Animals; Rabbits; Chromatography, Reverse-Phase; Diethylamines
PubMed: 38930798
DOI: 10.3390/molecules29122732 -
Molecules (Basel, Switzerland) Jun 2024Ultraviolet B (UVB) exposure can contribute to photoaging of skin. is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is...
Ultraviolet B (UVB) exposure can contribute to photoaging of skin. is rich in ursolic acid (UA), which is beneficial to the prevention of photoaging. Because UA is hardly soluble in water, the extract (COE) was obtained using water as the antisolvent to separate the components containing UA from the crude extract of . The effect of COE on UVB damage was assessed using . The results showed that COE could increase the lifespan and enhance the antioxidant enzyme activity of exposed to UVB while decreasing the reactive oxygen species (ROS) level. At the same time, COE upregulated the expression of antioxidant-related genes and promoted the migration of SKN-1 to the nucleus. Moreover, COE inhibited the expression of the downstream gene and the extension of the lifespan in mutants exposed to UVB, indicating that SKN-1 was required for COE to function. Our findings indicate that COE mainly ameliorates the oxidative stress caused by UVB in via the SKN-1/Nrf2 pathway.
Topics: Animals; Caenorhabditis elegans; Triterpenes; Ursolic Acid; Ultraviolet Rays; Plant Extracts; Caenorhabditis elegans Proteins; Oxidative Stress; Cornus; Antioxidants; Reactive Oxygen Species; Skin Aging; Transcription Factors; DNA-Binding Proteins; Longevity; NF-E2-Related Factor 2
PubMed: 38930783
DOI: 10.3390/molecules29122718