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ETHNOPHARMACOLOGICAL RELEVANCE: The safety assessment of herbal products is critical for their appropriate pharmacological applications. Garcinia cowa Roxb., commonly known as Cha-muang in Thai, has ethnopharmacological relevance for inflammation, infectious diseases, and diabetes. The leaf extracts of G. cowa have been extensively reported for their anticancer, anti-inflammatory, antimicrobial, and antioxidant effects. Notably, chamuangone is their major active constituent that contributes to various pharmacological properties. AIM OF THE STUDY: The current study aims to establish a standardized chamuangone enriched extract (CEE) and assess its acute and sub-acute toxicities in animal models. METHODOLOGY: CEE was established from G. cowa leaves using a microwave-assisted extraction (MAE), followed by fractionation and enrichment through silica gel vacuum and column chromatography. The concentration of chamuangone in the extract was quantified using a validated quantitative high-performance liquid chromatography (HPLC) method. The safety profiles of CEE were thoroughly evaluated in rodents according to the Organization for Economic Cooperation and Development (OECD) 425 and 407 guidelines. The effects on oxidative stress markers such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) levels were also evaluated in various organs. RESULTS: Based on the quantitative HPLC analysis, the CEE contained 73.0 ± 2.0% w/w of chamuangone. In the acute toxicity study, following up and down procedure the female rats were dosed with CEE at 1750 and 550 mg/kg body weight (b.w.), with CEE 1750 mg/kg b.w. was toxic, causing mortality, while CEE 550 mg/kg b.w. was deemed safe. An LD50 value was calculated according to the standard protocols, resulting in 970 mg/kg b.w. In histopathological examination, 550 mg/kg b.w. of CEE was safe in all the selected organs, while the 1750 mg/kg b.w. CEE treated rats exhibited toxic effects in histological tissues sections in the form of necrosis in the brain, cardiac muscle hypertrophy, liver inflammation, mild untoward effect in the spleen, fibrosis in the lungs, pancreatitis, pyelonephritis, and ovarian cyst. Administration of CEE at doses of 550 mg/kg b.w. (single dose) in the acute and 100 mg/kg b.w. (regularly 28-days) in the sub-acute toxicity studies significantly (p < 0.05) decreased levels of uric acid, triglycerides, and cholesterol. Importantly, the CEE (550 and 100 mg/kg b.w.) also significantly increased the levels of antioxidant enzymes (SOD, GSH, and CAT) and decreased MDA levels. Normal histopathology was observed in the sub-acute toxicity study in all treated groups. CONCLUSION: This study successfully concludes that CEE at a dose of 100 mg/kg b.w. is safe for therapeutic application or use as a chemopreventive functional food utilizing green extraction methods. However, chronic toxicity studies are further recommended to validate safety concerns over an extended period.
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α-Mangostin-rich extract (AME) shows promise as a functional ingredient for cancer chemotherapy. Here, we encapsulated AME in our originally designed antioxidant nanoparticles (NanoAOX) to increase its solubility and prevent oxidative degradation (AME@NanoAOX). In this study, two types of self-assembled polymers containing nitroxide radicals were engineered. These polymers were self-assembled into nanoscale particles in aqueous media, entrapping AME (abbreviated as AME@NanoAOX(B) and AME@NanoAOX(G)). These formulations considerably improved the stability of AME against oxidative degradation and exhibited different release profiles of α-mangostin under different pH conditions. Furthermore, AME-encapsulated nanoparticles exhibited potent cytotoxicity against various cancer cell lines, including human breast cancer (MCF-7), human lung cancer (A549), human colon cancer (Caco-2), human cervical cancer (HeLa), and human liver cancer (HepG2) cell lines, with minimal cytotoxicity in normal human mammary epithelial cells (hTERT-HME1), thus providing a high selectivity index (SI). These results indicated the promising feature of AME-encapsulated antioxidant nanoparticles (AME@NanoAOX) for cancer chemotherapy.
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Antioxidantes , Nanopartículas , Xantonas , Humanos , Xantonas/química , Xantonas/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Nanopartículas/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Estabilidad de Medicamentos , Células MCF-7 , Supervivencia Celular/efectos de los fármacosRESUMEN
Metabolic disorders pose significant global health challenges, necessitating innovative therapeutic approaches. This study focused on the multifaceted therapeutic potential of berberine-enriched extract (BEE) in mitigating metabolic impairment induced by streptozotocin (STZ) in a rat model and compared the effects of BEE with berberine (BBR) and metformin (MET) to comprehensively evaluate their impact on various biochemical parameters. Our investigation reveals that BEE surpasses the effects of BBR and MET in ameliorating metabolic impairment, making it a promising candidate for managing metabolic disorders. For this, 30 male Wistar rats were divided into five groups (n = 6): control (CN), STZ, STZ + MET, STZ + BBR, and STZ + BEE. The treatment duration was extended over 4 weeks, during which various biochemical parameters were monitored, including fasting blood glucose (FBG), lipid profiles, inflammation, liver and kidney function biomarkers, and gene expressions of various metabolizing enzymes. The induction of metabolic impairment by STZ was evident through an elevated FBG level and disrupted lipid profiles. The enriched extract effectively regulated glucose homeostasis, as evidenced by the restoration of FBG levels, superior to both BBR and MET. Furthermore, BEE demonstrated potent effects on insulin sensitivity, upregulating the key genes involved in carbohydrate metabolism: GCK, IGF-1, and GLUT2. This highlights its potential in enhancing glucose utilization and insulin responsiveness. Dyslipidemia, a common occurrence in metabolic disorders, was effectively managed by BEE. The extract exhibited superior efficacy in regulating lipid profiles. Additionally, BEE exhibited significant anti-inflammatory properties, surpassing the effects of BBR and MET in lowering the levels of inflammatory biomarkers (IL-6 and TNF-α), thereby ameliorating insulin resistance and systemic inflammation. The extract's superior hepatoprotective and nephroprotective effects, indicated by the restoration of liver and kidney function biomarkers, further highlight its potential in maintaining organ health. Moreover, BEE demonstrated potent antioxidant properties, reducing oxidative stress and lipid peroxidation in liver tissue homogenates. Histopathological examination of the pancreas underscored the protective effects of BEE, preserving and recovering pancreatic ß-cells damaged by STZ. This collective evidence positions BEE as a promising therapeutic candidate for managing metabolic disorders and offers potential benefits beyond current treatments. In conclusion, our findings emphasize the remarkable therapeutic efficacy of BEE and provide a foundation for further research into its mechanisms, long-term safety, and clinical translation.
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Bacterial contamination and infection widely affect the food, pharmaceutical and biomedical industries. Additionally, these bacteria developed resistance to synthetic antibiotics causing public health danger, globally. Natural plant extracts (NPE) are suitable alternatives to synthetic antibiotics to tackle antimicrobial resistance problems. Furthermore, a blend or combination of different NPEs exerts a wide spectrum of antimicrobial activity. Therefore, the combined effect of brazilin-rich extract (BRE) and lawsome methyl ether (LME) against infection-causing common bacteria were evaluated. BRE had a lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against most of the Gram-negative bacteria (Salmonella typhi, Salmonella typhimurium and Pseudomonas aeruginosa) while LME was active against most of the Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus, and Staphylococcus epidermidis). The combination of BRE and LME at 2:1 and 1:1 concentration significantly reduced the MIC value of each compound as compared to either BRE or LME concentration alone (P < 0.05). Further time-kill kinetics revealed a 3.0-3.5 log reduction in Gram-positive bacteria and a 2.5-3.0 log reduction in Gram-negative bacteria during 120 min of incubation, respectively. Therefore, a combination of BRE and LME was recommended as natural antibacterial to synthetic antibiotics for food and pharmaceutical applications.
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Curcuma longa extract and its marker curcuminoids have potential use in inflammatory conditions. However, curcuminoids solubility and bioavailability are major hindrances to their bioactivity. The current study investigated green extraction-based curcuminoids-enriched extract (CRE) prepared from C. longa and its cyclodextrin inclusion complexes, i.e., binary inclusion complexes (BC) and ternary inclusion complexes (TC), in complete Freund's adjuvant (CFA)-induced mice for their comparative anti-arthritic efficacy. CRE, BC, and TC (2.5 and 5 mg/kg) with the standard drug diclofenac sodium (13.5 mg/kg) were orally administered to mice for 4 weeks. Variations in body weight, hematological and biochemical parameters, along with gene expression analysis of arthritis biomarkers, were studied in animals. The histopathological analysis and radiographic examination of joints were also performed. CRE, BC and TC treatment significantly restored the arthritic index, histopathology and body weight changes. The concentration of C-reactive protein, rheumatoid factor and other liver function parameters were significantly recovered by curcuminoids formulations. The pro-inflammatory cytokines (NF-κB, COX-2, IL-6, IL-1ß, and TNF-α) gene expression was considerably (p < 0.001) downregulated, while on the other side, the anti-inflammatory genes IL-4 and IL-10 were upregulated by the use of CRE and its complexes. The concentration of antioxidant enzymes was considerably (P < 0.001) recovered by CRE, BC and TC with marked decrease in lipid peroxidation, erosion of bone, inflammation of joints and pannus formation in comparison to arthritic control animals. Therefore, it is concluded that green CRE and its cyclodextrin formulations with enhanced solubility could be considered as an applicable therapeutic choice to treat chronic polyarthritis.
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Artritis Experimental , Ratones , Animales , Adyuvante de Freund , Artritis Experimental/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Estrés Oxidativo , Citocinas/metabolismo , Biomarcadores/metabolismo , Peso CorporalRESUMEN
Curcuminoids, namely curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are the major active compounds found in Curcuma longa L. (turmeric). Although their suppressive effects on bone resorption have been demonstrated, their pharmacokinetic disadvantages remain a concern. Herein, we utilized solid dispersion of a curcuminoid-rich extract (CRE), comprising such curcuminoids, to prepare CRE-SD; subsequently, we performed liposome encapsulation of the CRE-SD to yield liposomal CRE-SD. In vitro release assessment revealed that a lower cumulative mass percentage of CRE-SD was released from liposomal CRE-SD than from CRE-SD samples. After culture of murine RANKL-stimulated RAW 264.7 macrophages, our in vitro examinations confirmed that liposomal CRE-SD may impede osteoclastogenesis by suppressing p65 and IκBα phosphorylation, together with nuclear translocation and transcriptional activity of phosphorylated p65. Blind docking simulations showed the high binding affinity between curcuminoids and the IκBα/p50/p65 protein complex, along with many intermolecular interactions, which corroborated our in vitro findings. Therefore, liposomal CRE-SD can inhibit osteoclastogenesis via the canonical NF-κB signaling pathway, suggesting its pharmacological potential for treating bone diseases with excessive osteoclastogenesis.
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BACKGROUND: Breast cancer is the highest incidence of all types of cancer in women, and the cancer metastasis process accounts for a majority of cancer deaths. Two major cannabinoids, Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), from Cannabis sativa are expected to have anti-cancer activity. This study aimed to investigate the effects of THC, CBD, and standardized cannabis extracts (F1, F2, and F3) on migration, invasion, and apoptosis of human breast cancer (MCF-7) cells. METHODS: Cell viability, survival, and apoptosis were determined using the MTT, clonogenic, and nuclear staining assays, respectively, while cancer cell migration and invasion were evaluated by the wound healing, trans-well, and filopodia assays. Western blot analysis was used to find out the mechanisms of the cannabinoids against MCF-7 cells. RESULTS: CBD, THC, and F1 inhibited filopodia formation, migration, and invasion of MCF-7 cells through suppressing the expression of the FAK, Akt, ERK1/2, p38MAPKs, and NF-κB upstream pathways, as well as inhibiting the Rac1/Cdc42 downstream pathways. In addition, CBD significantly inhibited the mTOR pathway. Furthermore, CBD and F1 induced apoptosis in MCF-7 cells via the Bcl-2/caspase-3 pathways. CONCLUSION: These results indicate that THC, CBD, and F1 have great abilities for preventing breast cancer cell metastasis in in vitro experiments.
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Neoplasias de la Mama , Cannabidiol , Cannabinoides , Cannabis , Femenino , Humanos , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Cannabidiol/farmacología , Cannabinoides/farmacología , Cannabis/metabolismo , Células MCF-7 , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismoRESUMEN
Our previous study uncovered potent inhibitory effects of two naphthoquinones from Impatiens balsamina, namely lawsone methyl ether (2-methoxy-1,4-naphthoquinone, LME) and lawsone (2-hydroxy-1,4-naphthoquinone), against α-glucosidase. This gave us the insight to compare the hypoglycemic and hypolipidemic effects of LME and lawsone in high-fat/high-fructose-diet- and nicotinamide-streptozotocin-induced diabetic rats for 28 days. LME and lawsone at the doses of 15, 30, and 45 mg/kg, respectively, produced a substantial and dose-dependent reduction in the levels of fasting blood glucose (FBG), HbA1c, and food/water intake while boosting the insulin levels and body weights of diabetic rats. Additionally, the levels of total cholesterol (TC), triglycerides (TGs), high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), aspartate transaminase (AST), alanine transaminase (ALT), creatinine, and blood urea nitrogen (BUN) in diabetic rats were significantly normalized by LME and lawsone, without affecting the normal rats. LME at a dose of 45 mg/kg exhibited the most potent antihyperglycemic and antihyperlipidemic effects, which were significantly comparable to glibenclamide but higher than those of lawsone. Furthermore, the toxicity evaluation indicated that both naphthoquinones were entirely safe for use in rodent models at doses ≤ 50 mg/kg. Therefore, the remarkable antihyperglycemic and antihyperlipidemic potentials of LME make it a promising option for future drug development.
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Despite the numerous treatment strategies used for Alzheimer's disease (AD), only a few cholinesterase inhibitor drugs, such as memantine, are effective in symptomatically relieving the hallmarks of AD, providing momentary recovery of memory and cognitive decline. These available drugs do not treat the underlying causes of AD, and their chronic use is associated with serious adverse effects and disease progression. Berberine is an isoquinoline alkaloid that has been reported to possess therapeutic potential against AD. Therefore, its activity was evaluated against an aluminum chloride (AlCl3)-induced AD rat model, and a berberine-enriched extract (BEE) was used to determine if its activity is equivalent to pure berberine (PB). The rats were administered 300 mg/kg of oral AlCl3 to induce AD and were then treated with oral PB at a dosage of 50 mg/kg, BEE at a dosage of 50 mg/kg, and rivastigmine at a dosage of 1 mg/kg as a standard drug for 21 days. In this study, various parameters were assessed to evaluate cognitive functions, such as behavioral analysis, antioxidant enzyme levels, acetylcholinesterase (AChE) activity, proinflammatory cytokine levels, real-time polymerase chain reaction (RT-PCR) analysis of different biomarkers (AChE, IL-1α, IL-1ß, BACE-1, TNF-α) linked to AD, and histopathological changes in the rats' brains. After 21 days, the disease control group showed a significant decline in cognitive function, decreased levels of antioxidant enzymes, upregulated activity of the AChE enzyme, increased levels of proinflammatory cytokines, and marked elevation in mRNA expression of AD-associated biomarkers. On the other hand, the treatment groups showed significant improvements in memory deficits, elevated levels of antioxidant enzymes, reduced levels of proinflammatory cytokines, decreased AChE activity, and significant downregulation of the expression of predefined biomarkers. Histological examination of the treatment groups showed less neuroinflammation and fewer amyloid plaques compared to the disease control group. In conclusion, both PB and BEE have comparable neuroprotective potential to mitigate the pathological hallmarks of AD. However, controlled clinical trials are needed to assess their efficacy and safety.
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Enfermedad de Alzheimer , Berberina , Ratas , Animales , Cloruro de Aluminio/toxicidad , Antioxidantes/metabolismo , Berberina/farmacología , Berberina/uso terapéutico , Acetilcolinesterasa/metabolismo , Enfermedades Neuroinflamatorias , Estrés Oxidativo , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Biomarcadores/metabolismoRESUMEN
BACKGROUND: Diabetes is a kind of metabolic syndrome (MetS) that seriously threatens human health globally. The leaf of star apple (Chrysophyllum cainito L.) is an incompletely explored folk medicine on diabetes. And, the effects and mechanisms on diabetes complicated glycolipid metabolism disorders are unknown till now. PURPOSE: This study aimed to investigate the constituents of star apple leaf polyphenol enriched-fraction (SAP), and elucidate their treatment effects and mechanism on diabetes and accompanied other MetS. METHODS: The components of SAP were tentatively identified by HPLC-Q-TOF-MS/MS. The antioxidant activity was determined by the scavenging of free radicals and hypoglycemic activities by inhibition of α-glucosidase in vitro. HepG2 cells were used for evaluating the alleviation effects of SAP on lipid accumulation. Streptozotocin and high-fat diet induced diabetic mice were grouped to evaluate the effects of different dosages of SAP. 16S rRNA was conducted to analysis gut microbiome-mediated glucose and lipid metabolism mechanism. RESULTS: It showed that myricitrin was one of the main active constituents of SAP. SAP not only showed low IC50 on -glucosidase (24.427± 0.626 µg/mL), OH·(3.680± 0.054 µg/mL) and ABTS· (9.155±0.234 µg/mL), but significantly induced the lipid accumulation in HepG2 cells (p < 0.05). SAP at 200 mg/kg·day significantly decreased the blood glucose, insulin and oral glucose tolerance test value (p < 0.05). The insulin resistance indexes and oxidative stress were alleviated after administration. SAP not only attenuated hepatic lipid deposition, but also reversed the hepatic glycogen storage. 16S rRNA sequencing results revealed that the interaction between SAP and gut microbiota led to the positive regulation of beneficial bacteria including Akkermansia, Unspecified S24_7, Alistipes and Unspecified_Ruminococcaceae, which might be one of the mechanisms of SAP on MetS. CONCLUSION: For the first time, this study explored the regulation effect of star apple leaf polyphenols on the hepatic glycolipid metabolism and studied the underlying mechanism from the view of gut microbiota. These findings indicated that SAP possesses great potential to serve as a complementary medicine for diabetes and associated MetS. It provided scientific evidence for folk complementary medicine on the treatment of diabetes-complicated multiple metabolic disorders.
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Diabetes Mellitus Experimental , Microbioma Gastrointestinal , Malus , Síndrome Metabólico , Ratones , Humanos , Animales , Síndrome Metabólico/tratamiento farmacológico , Glucosa/farmacología , ARN Ribosómico 16S/genética , Malus/genética , Malus/metabolismo , Diabetes Mellitus Experimental/metabolismo , Metabolismo de los Lípidos , Polifenoles/farmacología , Polifenoles/uso terapéutico , Espectrometría de Masas en Tándem , Glucolípidos , Hojas de la Planta , Dieta Alta en Grasa , Ratones Endogámicos C57BLRESUMEN
Objective: The purpose of this study was to (i) synthesize and develop an alkynyloxy derivative of lawsone as an antifungal spray and (ii) assess the antifungal spray's effectiveness in reducing the viability of Candida albicans (C. albicans) on polymethylmethacrylate (PMMA) specimens. Methods: Lawsone methyl ether (LME) and its derivative, 2-(prop-2-ynyloxy)naphthalene-1,4-dione (compound 1) were synthesized and characterized. The synthetic compounds were screened for antimicrobial activities against C. albicans using the microtiter broth dilution method to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). Compound 1 was further formulated as an antifungal spray in three concentrations (100, 200, and 400 µg/mL). C. albicans biofilms were developed for 48 h on PMMA specimens. The efficacy of using an antifungal spray for 1 and 3 min to remove biofilm was assessed using colony counting and scanning electron microscopy (SEM). Chlorhexidine gluconate (CHX), polident®, and distilled water were used as positive and negative control cleansing solutions, respectively. Results: LME and compound 1 showed comparable inhibition against C. albicans with a MIC of 25 µg/mL and MFC of 50 µg/mL. For immediate treatment, C. albicans was not detected on PMMA specimens when expose to 2% CHX and compound 1 (100, 200, and 400 µg/mL) antifungal spray for 3 min. However, after recolonization, a small number of viable cells were observed in denture soaked in compound 1 antifungal spray for 3 min group. Following recolonization, polident® and distilled water had comparable viable cell counts of C. albicans to the no treatment group. Scanning electron microscope (SEM) images revealed that CHX, polident®, and compound 1 caused cell damage in various forms. Conclusion: Denture spray containing synthetic alkynyloxy derivative of lawsone is a promising antifungal agent for C. albicans biofilm removal from the PMMA surface.
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Rhinacanthus nasutus has been traditionally used for skin infections, diabetes, inflammatory disorders and cancer therapies. Rhinacanthin-C, -D, and -N have been identified as its bioactive compounds. The content of active compounds in herbal raw materials and health products usually varies due to various factors, such as plant genetics, climate, and harvesting process. The present study aimed to determine the effect of harvesting factors, including part use and harvesting periods on rhinacanthin content of raw materials and health products of R. nasutus. Six parts of R. nasutus raw materials, i.e., leaves, flowers, roots, green twigs, brown twigs and aerial parts that separately harvested every two months together with two commercially available products of R. nasutus tea were extracted using a microwave-assisted extraction and subjected to quantitative HPLC analysis of rhinacanthin-C, -D, and -N. Among the plant parts, the roots contained the highest content of total rhinacanthins, followed by the leaves, in all every harvesting periods. While the other parts contained very low content of total rhinacanthins. In addition, the highest content of total rhinacanthins accumulated in roots (4.91 %, w/w) and leaves (4.42 %, w/w) were observed when they were harvested in September, while the lowest ones (3.73 % and 3.18 %, w/w, respectively) were found in March. In contrast, R. nasutus powders obtained from ten suppliers and two tea products contained very low content of total rhinacanthins and varied in the ranges of 0.14-0.55 %, w/w, which similar to those observed in the aerial part powders (0.27-0.53 %, w/w).
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Acanthaceae , Naftoquinonas , Extractos Vegetales , Polvos , TéRESUMEN
Parkinson's disease (PD) is slowly developing neurodegenerative disorder associated with gradual decline in cerebration and laboriousness to perform routine piece of work. PD imposed a social burden on society through higher medical cost and by loss of social productivity in current era. The available treatment options are expensive and associated with serious adverse effect after long term use. Therefore, there is a critical clinical need to develop alternative pharmacotherapies from natural sources to prevent and cure the pathological hall marks of PD with minimal cost. Our study aimed to scrutinize the antiparkinsonian potential of curcuminoids-rich extract and its binary and ternary inclusion complexes. In healthy rats, 1 mg/kg haloperidol daily intraperitoneally, for 3 weeks was used to provoke Parkinsonism like symptoms except control group. Curcuminoids rich extract, binary and ternary inclusion complexes formulations 15-30 mg/kg, L-dopa and carbidopa (100 + 25 mg/kg) were orally administered on each day for 3 weeks. Biochemical, histopathological and RT-qPCR analyses were conducted after neurobehavioral observations. Findings of current study indicated that all curcuminoids formulations markedly mitigated the behavioral abnormalities, recovered the level of antioxidant enzymes, acetylcholinesterase inhibitory activity and neurotransmitters. Histological analysis revealed that curcuminoids supplements stabilized the neuronal loss, pigmentation and Lewy bodies' formation. The mRNA expressions of neuro-inflammatory and specific PD pathological biomarkers were downregulated by treatment with curcuminoids formulations. Therefore, it is suggested that these curcuminoids rich extract, binary and ternary supplements should be considered as promising therapeutic agents in development of modern anti-Parkinson's disease medications.
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Diarilheptanoides , Enfermedad de Parkinson , Ratas , Animales , Diarilheptanoides/uso terapéutico , Haloperidol/farmacología , Haloperidol/uso terapéutico , Acetilcolinesterasa , Modelos Animales de Enfermedad , Enfermedad de Parkinson/tratamiento farmacológicoRESUMEN
Macrophages have important roles in the progression of inflammation. Ajania purpurea Shih. is a member of the Ajania Poljakor family that grows in Tibet (China). Extracts from plants in this genus have anti-bacterial and anti-inflammatory properties. However, there are few reports on the activity and mechanism of Ajania purpurea. Here, we confirmed the anti-inflammatory effect of Ajania purpurea Shih. ethanol extract (EAPS) by examining the levels of inflammatory factors in a mouse model of peritonitis and RAW264.7 cells. The main components of EAPS detected by LC-MS analysis included piperine and chlorogenic acid. In particular, in lipopolysaccharide (LPS)-induced RAW264.7 cells, EAPS inhibited the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW264.7 cells, lowered the levels of nitric oxide (NO) and prostaglandin E2 (PGE2), as well as the release of inflammatory factors such as tumor necrosis factor-alpha (TNF-α) and pro-inflammatory cytokines such as interleukin (IL)-1ß and IL-6. In addition, Western blot analysis and immunofluorescence staining verified that EAPS inhibited the activity of the nuclear factor-kappaB (NF-κB) pathway by reducing the nuclear translocation of the p65 subunit. Furthermore, in a mouse model of peritonitis, EAPS inhibited the release of inflammatory factors, as well as the recruitment of immune cells including neutrophils and macrophages. These findings indicated that EAPS suppressed LPS-induced inflammation via inhibiting the NF-κB pathway in RAW264.7 cells and mice with peritonitis. Thus, EAPS may be a viable therapeutic method for the treatment of inflammation and related disorders.
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Lipopolisacáridos , Peritonitis , Ratones , Animales , FN-kappa B , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Peritonitis/inducido químicamente , Peritonitis/tratamiento farmacológico , Dinoprostona , Modelos Animales de Enfermedad , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
The present study evaluated the effects of water-soluble curcuminoid-rich extract in a solid dispersion form (CRE-SD) on goat sperm qualities and sperm protein CSNK2A2 expression during liquid storage. Semen was collected from five fertile goats, using an artificial vagina. Ejaculates with a motility above 70% were cooled to 4 °C using TRIS-citric acid-fructose diluent with 10% egg yolk containing various concentrations of CRE-SD (0, 0.1, 1, 10 and 100 µg/mL). Chilled sperm were evaluated for sperm characteristics, casein kinase II catalytic subunit alpha (CSNK2A2) protein level and oxidative status up to 15 days. After 12 days of preservation, sperm motility, viability, acrosomal integrity and mitochondrial activity were significantly higher in the group preserved with 10 µg/mL CRE-SD as compared with the control group. Supplementation of CRE-SD at this concentration was also able to conserve the CSNK2A2 a significantly higher than that in control group until 9 days of cold storage, possibly by reducing oxidative stress. The molecular mass of the sperm CSNK2A2 protein detected in this study was 37 kDa; it was mostly located in the post-acrosomal region, midpiece and flagellum. These results demonstrate the possibility to use the CRE-SD as a natural antioxidant during liquid semen storage in goats.
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Preservación de Semen , Semen , Animales , Femenino , Masculino , Motilidad Espermática , Preservación de Semen/veterinaria , Preservación de Semen/métodos , Cabras , Criopreservación/métodos , Diarilheptanoides/farmacología , Longevidad , Agua , Quinasa de la Caseína II/farmacología , Dominio Catalítico , Espermatozoides , Estabilidad ProteicaRESUMEN
Berberine-rich extract (BRE) prepared from Berberis lycium root bark using green extraction approach and its marker compound berberine has a broad spectrum of clinical applications. Berberine's potential pharmacological effects include anticancer, antidiarrheal, antidiabetic, antimicrobial and anti-inflammatory activities. In current work, BRE and berberine were evaluated for their therapeutic prospects in inflammation models. The comparative effect of BRE and berberine against inflammation was determined through in vitro chemiluminescence technique. The in vivo anti-inflammatory evaluation of BRE and berberine (25, 75, and 125 mg/kg) compared to diclofenac (10 mg/kg) was performed in carrageenan and formaldehyde-induced inflammation in Wistar rats. Histopathological and biochemical studies were conducted to find the comparative anti-inflammatory potential of BRE and berberine on pathological hallmarks induced by formaldehyde. Moreover, the modulatory effects on inflammatory biomarkers were also investigated through qPCR. ELISA (enzyme-linked immunoassay test assay) was performed to investigate the expression of pathological protein biomarkers like TNF-α and IL-6 and levels of antioxidant enzymes were estimated in liver homogenates. Both BRE and berberine markedly (p < .001) reduced paw diameter and inflammation in carrageenan and formaldehyde-induced inflammation. The levels of antioxidant enzymes were recovered (p < .001) by BRE and berberine treatments, and compared to the formaldehyde-treated inflammation model. Both BRE and berberine remarkably downregulated the mRNA and protein expression of inflammatory biomarkers. BRE similar to berberine mitigated the level of antioxidant enzymes in liver homogenate. The undertaken study suggests that BRE, a natural, green, and therapeutically bioequivalent to berberine could be used as an economical phytomedicine in the treatment of inflammatory disorders. PRACTICAL APPLICATIONS: Anti-inflammatory drugs like NSAIDS are associated with serious adverse effects like gastrointestinal ulcer, worsening of preexisting cardiovascular disorders, and renal failure. Therefore, there is a constant demand to develop novel, inexpensive therapeutic strategies to treat the inflammatory disorder with the least harmful effects. Pure phytochemicals with anti-inflammatory potential are costly and hard to isolate, therefore green microwave-assisted extraction technique is developed to get the rich bioequivalent extract. Berberis lycium a medicinal plant with berberine as a major bioactive constituent, has wide acceptance in traditionally used medicine and as food. Pharmacological studies revealed its hepatoprotective, anticancer, antidiabetic, and antihypertensive activities. BRE was prepared by green microwave-assisted extraction and enrichment by resin column to get a higher yield of berberine. The comparative anti-inflammatory effect of BRE and berberine was determined by in vitro and in vivo studies. Results obtained from this experimental work contribute beneficial guidance that reinforces the use of the BRE to treat inflammatory disorders.
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Berberina , Extractos Vegetales , Ratas , Animales , Carragenina/efectos adversos , Extractos Vegetales/química , Antioxidantes/química , Berberina/farmacología , Ratas Wistar , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Hipoglucemiantes/farmacología , FormaldehídoRESUMEN
Two major cannabinoids of cannabis, namely cannabidiol (CBD) and tetrahydrocannabinol (THC) have been reportedly used as alternative medicine for diabetes treatment in both pre-clinical and clinical research. However, their mechanisms of action still remain unclear. Therefore, this study aimed to evaluate the α-glucosidase inhibitory activity of THC, CBD and the standardized cannabinoid extracts. Based on in silico studies, THC generated hydrogen bonding and Van der Waals interactions, while CBD exhibited only Van der Waals interactions with functional residues of target α-glucosidase protein, with good binding energies of -7.5 and -6.9 kcal/mol, respectively. In addition, both of them showed excellent pharmacokinetic profiles with minor toxicity in terms of tumorigenic and reproductive effects. In addition, the enzyme based in vitro assay on α-glucosidase revealed that THC and CBD exhibited good inhibitory activity, with the IC50 values of 3.0 ± 0.37 and 5.5 ± 0.28 µg/ml, respectively. These were better than the standard drug, acarbose (IC50 of 488.6 ± 10.23 µg/ml). Furthermore, two standardized cannabinoid extracts, SCE-I (C. sativa leaf extract) and SCE-II (C. sativa inflorescence extract) exhibited stronger inhibitory activity than THC and CBD, with the IC50 values of 1.2 ± 0.62 and 0.16 ± 0.01 µg/ml, respectively. The present study provides the first evidence that the standardized cannabinoid extracts containing THC and CBD have greater potential than CBD and THC in application as an α-glucosidase inhibitor.
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A simple and validated HPLC method for quantitative analysis of [6]-gingerol in ginger extracts was established. The optimum HPLC conditions involved a TSK-gel ODS-80 Ts column (5 µm, 4.6 ´ 250 mm) eluted with acetonitrile and 1% aqueous acetic acid (48:52, v/v), at 30ºC, with a flow rate of 1 mL/min and a quantitative UV detection at 280 nm. A good selectivity, linearity (R² of 1.0000), accuracy (Recovery of 96.7-103.2%), intraday- and interday-precision (Relative standard deviation (RSD) of less than 2% and 5%, respectively) and sensitivity (LOD and LOD of 0.48 and 0.80 µg/mL, respectively) were obtained. A microwave-assisted extraction was used for preparation of [6]-gingerol enriched ginger extracts. Based on HPLC analysis, the concentrations of [6]-gingerol of the extracts obtained from 20% v/v glycerin in ethanol (0.45 mg/mL) as well as 20% v/v natural deep eutectic solvents (NADES) of sucrose & citric acid in ethanol (0.43 mg/mL) were not significantly different from ethanol (0.42 mg/mL). However, glycerin (20% v/v) or NADES of sucrose & citric acid (20% v/v) might be used as the alternative green solvents for preparation of [6]-gingerol extract that could be directly used for formulation of anti-nausea and vomiting pastilles.
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Zingiber officinale , Catecoles , Cromatografía Líquida de Alta Presión , Disolventes Eutécticos Profundos , Etanol , Alcoholes Grasos , Glicerol , Solventes , SacarosaRESUMEN
This study investigated the antioxidant activities, enzyme inhibitory activities and the interaction mechanisms of artocarpin and α-mangostin on α-amylase and α-glucosidase. Results showed that artocarpin and α-mangostin had obvious antioxidant activities and inhibitory activities on α-glucosidase and α-amylase. The inhibitions of the two compounds on α-glucosidase were reversible and non-competitive according to the kinetics studies. Fluorescence intensity measurements indicated that the interaction mechanisms between the inhibitors and the two enzymes were static processes. Isothermal titration calorimetry (ITC) analysis showed that the bindings between the inhibitors and the enzymes complex were all spontaneous. The main driving forces between α-mangostin and artocarpin with α-glucosidase might be hydrogen bonds and electrostatic interactions, respectively. While the forces between the two inhibitors and α-amylase might be hydrophobic interactions. Furthermore, molecular docking results showed that artocarpin and α-mangostin could bind to the allosteric site of the two enzymes, except for artocarpin in the active site pocket of α-amylase. All the results indicated that artocarpin and α-mangostin might be promising candidates for hypoglycemic functional products.
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alfa-Amilasas , alfa-Glucosidasas , Antioxidantes/química , Antioxidantes/farmacología , Inhibidores de Glicósido Hidrolasas/química , Hipoglucemiantes/farmacología , Cinética , Lectinas de Unión a Manosa , Simulación del Acoplamiento Molecular , Lectinas de Plantas , Xantonas , alfa-Amilasas/química , alfa-Glucosidasas/metabolismoRESUMEN
Alzheimer's disease (AD) is a slowly progressive brain degenerative disorder which gradually impairs memory, thinking, and ability to perform easy routine tasks. This degenerative disorder mainly targets the elderly people and has imposed an endemic burden on society. Hence, there is a crucial need to investigate the efficacious herbal pharmacotherapies that can effectively mitigate and prevent the pathological hallmarks of AD. The current study aims to explore the potential efficacy of curcuminoid-rich extract (CRE) and its ternary complex (TC). Experimental rodents were administered with AlCl3 (300 mg/kg) to induce AD and treated with rivastigmine, curcuminoid crude extract, CRE, and TC orally for three consecutive weeks. Neurobehavioral, biochemical, and histopathological studies were performed from the last week of the study period. The mRNA expression of different pathological biomarkers was estimated by RT-qPCR analysis. The results of the study suggested that CRE and TC significantly improved the behavioral, biochemical parameters and acetylcholinesterase inhibitory activity in treatment groups. Histological analysis was also carried out indicating that the neurodegenerative changes and neuronal loss were stabilized by CRE and TC supplementation. CRE and TC supplementation remarkably downregulated the interleukin-1α, tumor necrosis factor-α, interleukin-1ß, acetylcholinesterase, and ß-secretase pathological gene expression. Hence, it was concluded that CRE and TC may act as promising candidates in the prevention of AD via numerous underlying signaling pathways.