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Serum metabolic profiling. (A) Heatmap of metabolic profiles at different time points after cobra venom intra-ION injection. (B) Heatmap of metabolic profiles in different groups of rats.
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Background
Depression is a prevalent and complex psychiatric disorder with high incidence in patients with chronic pain. The underlying pathogenesis of chronic pain-induced depression is complicated and remains largely unclear. An integrated analysis of endogenous substance-related metabolisms would help to understand the molecular mechanism of chr...
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Docetaxel-based therapy has been applied to kill cancers including lung and breast cancers but frequently causes peripheral neuropathy such as mechanical allodynia. Lack of effective drugs for chemotherapy-induced peripheral neuropathy (CIPN) treatment leads us to find novel drugs. Here, we investigated whether and how novel anticancer herbal presc...
Citations
... It is commonly associated with different metabolic disorders as hypertension, dyslipidaemia, obesity and insulin resistance (Khatiwada et al., 2016). Previous studies on the mechanisms of hypothyroidism were mainly focused on physiological causes of the disorder, however, it has been recently hypothesized that some metabolites are considered as sensitive markers of physiological functions, which may refer to the non-typical molecular variations related to hypothyroidism (Zhang et al., 2020) Consequently, changes in these serum metabolites levels could play crucial roles in the pathological pathways involved in hypothyroidism. Since, metabolomics as a recent developing "omics" refer to qualitative and quantitative analysis of small metabolites, it may significantly help in the identification of the metabolic profiling changes and unveiling the details of the basic pathways influenced by various diseases including hypothyroidism. ...
Abstract
Ethnopharmacological relevance
Saussurea costus (Falc.) Lipschitz. is one of the most reputed medicinal plants as a traditional medicine in the Arab and Middle East regions in the treatment of thyroid disorders, however, more investigations are needed to fully understand its effectiveness and mechanism of action.
Aim of the study
The primary objective of the study was to assess the impact of Saussurea costus (COST) on the metabolic profiles of propylthiouracil (PTU)-induced hypothyroidism in rats. This involves a comprehensive examination of serum metabolites using UPLC/QqQ-MS analysis aiming to identify differential metabolites, elucidate underlying mechanisms, and evaluate the potential pharmacological effect of COST in restoring metabolic homeostasis.
Materials and methods
Hypothyroidism was induced in female Sprague-Dawley rats by oral administration of propylthiouracil (PTU). UPLC/QqQ MS analysis of serum samples from normal, PTU, and PTU + COST rats was utilized for annotation of intrinsic metabolites with the aid of online Human metabolome database (HMDB) and extensive literature surfing. Multivariate statistical analyses, including orthogonal partial least squares discriminant analysis (OPLS-DA), discerned variations between the different groups. Serum levels of T3, T4 and TSH in addition to arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels in thyroid gland tissues; Phospholipase A2 group IIA (PLA2G2A), and lipoprotein lipase (LPL) in liver tissues were assessed by specific ELISA kits. Gene expression for key proteins of the primary evolved pathwayswere quantified by one-step qRT-PCR technique. Histopathological evaluation of thyroid gland tissue was performed by an investigator blinded to the experimental group using light microscope.
Results
Distinct clustering in multivariate statistical analysis models indicated significant variations in serum chemical profiles among normal, disease, and treated groups. VIP values guided the selection of differential metabolites, revealing significant changes in metabolite concentrations. Subsequent to COST treatment, 43 differential intrinsic metabolites exhibited a notable tendency to revert towards normal levels. Annotated metabolites, such as lysophosphatidylcholine (LPC), L-acetylcarnitine, gamma-glutamylserine, and others, showed differential regulation in response to PTU and subsequent S. costus treatment. Notably, 21 metabolites were associated with polyunsaturated fatty acids (PUFAs) biosynthesis, arachidonic acid (ARA) metabolism, and glycerophospholipid metabolism exhibited significant changes on conducting metabolic pathway analysis.
Conclusions
COST improves PTU-induced hypothyroidism by regulating biosynthesis of PUFAs signified by n-3/n-6, ARA and glycerophospholipid metabolism. The study provides us a novel mechanism to explain the improvement of hypothyroidism and associated dyslipidemia by COST, depicts a metabolic profile of hypothyroidism, and gives us another point cut for further exploring the biomarkers and pathogenesis of hypothyroidism.
... Curcumin, demethoxycurcumin, and bisdemethoxycurcumin are the three major substances [6]. Due to its putative anti-inflammatory and antioxidant properties [7,8], curcumin has been widely verified to be active in treating different conditions, including anxiety, hyperlipidemia, inflammatory and oxidative disorders, arthritis, metabolic syndrome, and cancers, including lung, bladder, and breast cancers [9][10][11][12][13]. ...
(1) Background: A molecular hybridization docking approach was employed to develop and detect a new category of naturally activated compounds against Culex pipiens as acetylcholinesterase inhibitors via designing a one-pot multicomponent nano-delivery system. (2) Methods: A nanostructure lipid carrier (NLC), as a second generation of solid lipid nanoparticles, was used as a carrier to deliver the active components of curcumin (Cur), geraniol (G), and linalool (L) in one nanoformulation after studying their applicability in replacing the co-crystallized ligand imidacloprid. (3) Results: The prepared nanostructure showed spherical-shaped, polydisperse particles ranging in size from 50 nm to 300 nm, as found using a transmission electron microscope. Additionally, dynamic light scattering confirmed an average size of 169 nm and a highly stable dispersed solution, as indicated by the zeta potential (−38 mV). The prepared NLC-Cur-LG displayed competitive, high-malignancy insecticidal activity against fourth instar C. pipiens with an elevated rate of death of 0.649 µg/mL. The treatment, due to the prepared nanostructure, affects oxidative stress enzymes, e.g., hydrogen peroxide (4 ppm), superoxide dismutase (SOD) (0.03 OD/mg), and protein carbonyl (0.08 OD/mg), and there are observable upward and downward fluctuations when using different concentrations of NLC-Cur-LG, suggesting significant problems in its foreseeable insecticidal activity. The acetylcholinesterase activity was assessed by an enzyme inhibition assay, and strengthened inhibition occurred due to the encapsulated NLCs (IC50 = 1.95 µg/mL). An investigation of the gene expression by Western blotting, due to treatment with NLC-Cur-LG, revealed a severe reduction of nearly a quarter of what was seen in the untreated group. As a preliminary safety step, the nanoformulation’s toxicity against normal cell lines was tested, and a reassuring result was obtained of IC50 = 158.1 µg/mL for the normal lung fibroblast cell line. (4) Conclusions: the synthesized nanoformulation, NLC-Cur-LG, is a useful insecticide in field conditions.
... The mouse model of trigeminal neuralgia was established by pT-ION, per our previously established methodology [24]. In the extant literature, chronic constriction injury (CCI) of the ION [25,26] and cobra venom-induced models [27] are widely used. However, the precision of CCI surgery is difficult to standardize. ...
Objective:
Cognitive impairment, one of the most prevalent complications of trigeminal neuralgia, is troubling for patients and clinicians due to limited therapeutic options. Curcumin shows antinociception and neuroprotection pharmacologically, suggesting that it may have therapeutic effect on this complication. This study aimed to investigate whether curcumin alleviates orofacial allodynia and improves cognitive impairment by regulating hippocampal CA1 region synaptic plasticity in trigeminal neuralgia.
Methods:
A mouse model of trigeminal neuralgia was established by partially transecting the infraorbital nerve (pT-ION). Curcumin was administered by gavage twice daily for 14 days. Nociceptive thresholds were measured using the von Frey and acetone test, and the cognitive functions were evaluated using the Morris water maze test. Dendritic spines and synaptic ultrastructures in the hippocampal CA1 area were observed by Golgi staining and transmission electron microscopy.
Results:
Curcumin intervention increased the mechanical and cold pain thresholds of models. It decreased the escape latency and distance to the platform and increased the number of platform crossings and dwell time in the target quadrant of models, and improved spatial learning and memory deficits. Furthermore, it partially restored the disorder of the density and proportion of dendritic spines and the abnormal density and structure of synapses in the hippocampal CA1 region of models.
Conclusion:
Curcumin alleviates abnormal orofacial pain and cognitive impairment in pT-ION mice by a mechanism that may be related to the synaptic plasticity of hippocampal CA1, suggesting that curcumin is a potential strategy for repairing cognitive dysfunction under long-term neuropathic pain conditions.
... As a consequence, it is currently used to treat neurological disorders, oxidative and inflammatory diseases, metabolic syndrome, arthritis, anxiety, hyperlipidemia, and numerous cancers (including breast, bladder, and lung cancer). (Kalman, 2017;Wu et al., 2016;Zhang et al., 2020;Shen et al., 2021). ...
Antibiotics have the potential to have both direct and indirect detrimental impacts on animal and human health. For instance, antibiotic residues and pathogenic resistance against the drug are very common in poultry because of antibiotics used in their feed. It is necessary to use natural feed additives as effective alternatives instead of synthetic antibiotics. Curcumin, a polyphenol compound one of the natural compounds from the rhizomes of turmeric (Curcuma spp.) and has been suggested to have several therapeutic benefits in the treatment of human diseases. Curcumin exhibited some positive responses such as growth promoter, antioxidant, antibacterial, antiviral, anticoccidial, anti-stress, and immune modulator activities. Curcumin played a pivotal role in regulating the structure of the intestinal microbiome for health promotion and the treatment of intestinal dysbiosis. It is suggested that curcumin alone or a combination with other feed additives could be a dietary strategy to improve poultry health and productivity.
... Together, these findings suggest that curcumin suppresses increased cytosolic mtDNA level and downstream type I IFN expression in PSNL mice by inhibiting hippocampal mitochondrial dysfunction, resulting in effects on anxiety-like behaviors in particular. Previous studies have reported that oral curcumin administration in animal models of depression leads to improved anxiodepressive-like behaviors through BDNF expression, inhibition of the NLRP3 inflammasome, and antioxidant effects (da Silva Marques et al., 2021;Madiha and Haider, 2019;Naqvi et al., 2019;Xu et al., 2006;Zhang et al., 2020;Zhang et al., 2019). Curcumin has a wide range of effects; it is thus very likely that actions other than improvements in mitochondrial dysfunction are involved in the effects of curcumin on anxiodepressive-like behaviors in the current study. ...
Clinical evidence indicates that major depression is a common comorbidity of chronic pain, including neuropathic pain; however, the cellular basis for chronic pain-mediated major depression remains unclear. Mitochondrial dysfunction induces neuroinflammation and has been implicated in various neurological diseases, including depression. Nevertheless, the relationship between mitochondrial dysfunction and anxiodepressive-like behaviors in the neuropathic pain state remains unclear. The current study examined whether hippocampal mitochondrial dysfunction and downstream neuroinflammation are involved in anxiodepressive-like behaviors in mice with neuropathic pain, which was induced by partial sciatic nerve ligation (PSNL). At 8 weeks after surgery, there was decreased levels of mitochondrial damage-associated molecular patterns, such as cytochrome c and mitochondrial transcription factor A, and increased level of cytosolic mitochondrial DNA in the contralateral hippocampus, suggesting the development of mitochondrial dysfunction. Type I interferon (IFN) mRNA expression in the hippocampus was also increased at 8 weeks after PSNL surgery. The restoration of mitochondrial function by curcumin blocked the increased cytosolic mitochondrial DNA and type I IFN expression in PSNL mice and improved anxiodepressive-like behaviors. Blockade of type I IFN signaling by anti-IFN alpha/beta receptor 1 antibody also improved anxiodepressive-like behaviors in PSNL mice. Together, these findings suggest that neuropathic pain induces hippocampal mitochondrial dysfunction followed by neuroinflammation, which may contribute to anxiodepressive-behaviors in the neuropathic pain state. Improving mitochondrial dysfunction and inhibiting type I IFN signaling in the hippocampus might be a novel approach to reducing comorbidities associated with neuropathic pain, such as depression and anxiety.
... Curcumin is reported to have effects as an antioxidant and anti-inflammatory agent (12)(13)(14). As a consequence, it has been used to treat oxidative and inflammatory disorders, metabolic syndrome, arthritis, anxiety, hyperlipidemia, cancers (i.e., Lung cancer, bladder cancer, and breast cancer), and neurological disorders (12,(15)(16)(17)(18)(19)(20). Curcumin also possesses nutritional and insecticide properties improving poultry and livestock animal's production performances and broad-spectrum activity against insects that damage the agricultural crops and can transfer diseases to human. ...
Plant-based natural products are alternative to antibiotics that can be employed as growth promoters in livestock and poultry production and attractive alternatives to synthetic chemical insecticides for insect pest management. Curcumin is a natural polyphenol compound from the rhizomes of turmeric (Curcuma spp.) and has been suggested to have a number of therapeutic benefits in the treatment of human diseases. It is also credited for its nutritional and pesticide properties improving livestock and poultry production performances and controlling insect pests. Recent studies reported that curcumin is an excellent feed additive contributing to poultry and livestock animal growth and disease resistance. Also, they detailed the curcumin's growth-inhibiting and insecticidal activity for reducing agricultural insect pests and insect vector-borne human diseases. This review aims to highlight the role of curcumin in increasing the growth and development of poultry and livestock animals and in controlling insect pests. We also discuss the challenges and knowledge gaps concerning curcumin use and commercialization as a feed additive and insect repellent.
... Metabolomics assays has been used to study the metabolic patterns underpinning depression caused by TN in a cobra venom intra-ION induced TN rodent model. Curcumin therapy in rats with TN may reduce mechanical allodynia and depressing actions through modulating metabolites and metabolic pathways [55]. ...
Trigeminal neuralgia (TN), a long-term disorder affecting the trigeminal nerve, is a form of debilitating neuropathic pain. Although the underlying pathogenesis of TN is debatable, loss of myelin along the trigeminal nerve due to direct compression from a blood vessel or secondary to other conditions such as multiple sclerosis or stroke is thought to be the principal cause. Paroxysmal sporadic pain, with unilateral onset, is the main phenomenon of TN. TN is typically diagnosed clinically. Medications, surgery, and complementary techniques are among the current therapy options for altering the neural circuits associated with TN. Nevertheless, anti-epileptic and tricyclic antidepressant medications are recognized as first-line treatments, and surgical treatment may be required for patients who have not obtained a therapeutic effect with at least three medications, have experienced intolerable side effects, or have symptoms that are not resolving. Stimulation of brain regions is an emerging off-label technique that has the potential to offer pain relief from TN, but sufficient data and more extensive studies on both animals and humans are yet to be published. More specifically, convenient diagnostic techniques and affordable treatment modalities for TN have become crucial needs in order to reduce the psychological and socio-economical losses caused by TN.
... In addition, several models of MDD were used, most of them (21) The antidepressant efficacy of curcumin in modulating depressive behavior in different animal models has been shown in a large number of behavioral studies. Most of the studies reported improved performance in the forced swimming test [35][36][37][38][39][40][41][42][43][44][45][46][47][48], increased locomotor activity in the open field test [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64], decreased anxiety in the elevated plus maze test [57,59,[64][65][66], improved anhedonia in the sucrose preference test [51,52,54,56,58,62,[67][68][69][70][71][72][73][74][75][76], improved short and long-term memory in the passive avoidance test [49,50,55] and water maze test [54,60,77], reduced escape response in the shuttle-box test [78], attenuated the effort-related abnormalities in a choice procedure test [79], and reduced stress in the tail suspension test [50,64,66,69,[80][81][82][83][84][85][86][87][88]. Only one study found no improvements in anxiety, as measured by the open field and elevated plus maze tests, nor in "depressive-like" states, as measured by the forced swimming test [89]. ...
... Furthermore, the BDNF is incremented by curcumin treatment [36,39,47,51,54,58,66,67,77,78,90]. Other effects of curcumin have been described in different animal models of depression, such as an interaction with glutamate N-Methyl-D-Aspartate (NMDA) receptors [37], an inhibition of Ca +2 channels [74], an increased level of corticosterol and cortisone in plasma [64], or an altered lipid metabolism [75], or an upregulation of the insulin receptor IRS-1 and protein kinase-B (PKB) in the liver [73]. In contrast, only one study reported no effects of curcumin, regarding its interaction with the benzodiazepine site on gamma-aminobutyric acid (GABA) receptor [89]. ...
Curcumin is a polyphenol extracted from the rhizome of the turmeric plant. Beyond its common use as a culinary spice in Eastern Asia, curcumin has been proposed as a therapeutic compound due to its antioxidant, anti-inflammatory and neuroprotective properties. Thus, its efficacy has been evaluated in various inflammatory-based psychiatric disorders, such as schizophrenia, depression, or autism. Our aim is to review those preclinical and clinical studies carried out in psychiatric disorders whose therapeutic approach has involved the use of curcumin and, therefore, to discern the possible positive effect of curcumin in these disorders. Preclinical studies and completed clinical trials of curcumin for psychiatric disorders published from January 2005 to October 2021 were identified through searching relevant databases until 31st October 2021. Sixty-five preclinical studies and 15 clinical trials and open-label studies were selected. Results showed a bias toward studies in depression and, to a lesser extent, schizophrenia. In all disorders, the results were positive in reducing psychiatric deficits. Despite the considerable number of beneficial outcomes reported, the small number of trials and the heterogeneity of protocols make it difficult to draw solid conclusions about the real potency of curcumin in psychiatric disorders.
... These results suggest the involvement of decreased IL-10 expression in DRG in DNP mice, similar to that observed in chronic constriction injury and partial sciatic ligation neuropathic pain models. Although we found that only the IL-10 gene was directly involved in pain, a report indicated that curcumin alleviated chronic pain induced-depression by modulating glycerophospholipid metabolism and ether lipid metabolism (Zhang et al. 2020). These findings suggested that genes involved in "glycerophospholipid metabolism" and "ether lipid metabolism," significantly enriched pathways in our research, might also be involved in pain. ...
DNA methylation and demethylation play an important role in neuropathic pain. In general, DNA methylation of CpG sites in the promoter region impedes gene expression, whereas DNA demethylation contributes to gene expression. Here, we evaluated the methylation status of CpG sites in genomic DNA promoter regions in dorsal root ganglions (DRGs) of diabetic neuropathic pain (DNP) mice. In our research, streptozotocin (STZ) was intraperitoneally injected into mice to construct DNP models. The DNP mice showed higher fasting blood glucose (above 11.1 mmol/L), lower body weight, and mechanical allodynia than control mice. Whole-genome bisulfite sequencing (WGBS) revealed an altered methylation pattern in CpG sites in the DNA promoter regions in DRGs of DNP mice. The results showed 376 promoter regions with hypermethylated CpG sites and 336 promoter regions with hypomethylated CpG sites. In addition, our data indicated that altered DNA methylation occurs primarily on CpG sites in DNA promoter regions. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially methylated CpG sites annotated genes were involved in activities of the nervous and sensory systems. Enrichment analysis indicated that genes in these pathways contributed to diabetes or pain. In conclusion, our study enriched the role of DNA methylation in DNP.
... [29] <8> Curcumin/po/mech., spon., mech. [25,96], Electro-acupuncture/spon. [97], Pregabalin/po/spon spon. [26,97] <9> Dexamethasone/ip/mech. ...
This review highlights potential molecular targets for treating neuropathic orofacial pain based on current findings in animal models. Preclinical research is currently elucidating the pathophysiology of the disease and identifying the molecular targets for better therapies using animal models that mimic this category of orofacial pain, especially post-traumatic trigeminal neuropathic pain (PTNP) and primary trigeminal neuralgia (PTN). Animal models of PTNP and PTN simulate their etiologies, that is, trauma to the trigeminal nerve branch and compression of the trigeminal root entry zone, respectively. Investigations in these animal models have suggested that biological processes, including inflammation, enhanced neuropeptide-mediated pain signal transmission, axonal ectopic discharges, and enhancement of interactions between neurons and glial cells in the trigeminal pathway, are underlying orofacial pain phenotypes. The molecules associated with biological processes, whose expressions are substantially altered following trigeminal nerve damage or compression of the trigeminal nerve root, are potentially involved in the generation and/or exacerbation of neuropathic orofacial pain and can be potential molecular targets for the discovery of better therapies. Application of therapeutic candidates, which act on the molecular targets and modulate biological processes, attenuates pain-associated behaviors in animal models. Such therapeutic candidates including calcitonin gene-related peptide receptor antagonists that have a reasonable mechanism for ameliorating neuropathic orofacial pain and meet the requirements for safe administration to humans seem worth to be evaluated in clinical trials. Such prospective translation of the efficacy of therapeutic candidates from animal models to human patients would help develop better therapies for neuropathic orofacial pain.
