RESUMEN
Sesamol (SM), a well-known component isolated from sesame seeds (Sesamum indicum), used in traditional medicines in treating numerous ailments. However, numerous molecular investigations revealed the various mechanisms behind its activity, emphasizing its antiproliferative, anti-inflammatory, and apoptosis-inducing properties, preventing cancer cell spread to distant organs. In several cells derived from various malignant tissues, SM-regulated signal transduction pathways and cellular targets have been identified. This review paper comprehensively describes the anticancer properties of SM and SM-viable anticancer drugs. Additionally, the interactions of this natural substance with standard anticancer drugs are examined, and the benefits of using nanotechnology in SM applications are explored. This makes SM a prime example of how ethnopharmacological knowledge can be applied to the development of contemporary drugs.
Asunto(s)
Benzodioxoles , Fenoles , Humanos , Benzodioxoles/farmacología , Fenoles/farmacología , Fenoles/química , Animales , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos/farmacología , Antineoplásicos/química , Apoptosis/efectos de los fármacosRESUMEN
A multi-herbal combination (MHC) of five herbs, namely Punica granatum L., Putranjiva roxburghii Wall., Swertia chirata Buch.-Ham., Tinospora cordifolia (Willd.) Miers and Trigonella corniculata L. was assessed against the paracetamol-induced acute hepatotoxicity in female Wistar rats. The animals were randomly assorted into seven groups with six animals in each group. The rats were pre-treated with MHC (50, 100, and 200 mg/kg bw) and silymarin (50 mg/kg bw) once daily for seven consecutive days via oral route followed by administration of paracetamol (3 g/kg bw) on day 7, an hour after the last administration of MHC and silymarin. It was observed that MHC administration significantly (p ≤ 0.05) overturned the paracetamol-induced increase in serum liver function biomarkers (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and total bilirubin), phase I reaction enzymes (NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase), and oxidant biomarkers (lactate dehydrogenase, lipid peroxidation, lipid hydroperoxides, and protein content). MHC administration also reinstated the paracetamol-induced significant decrease (p ≤ 0.05) in haematological indices (haematocrit, haemoglobin, red and white blood cells, and platelets), phase II reaction enzymes (glutathione-S-transferase and DT-diaphorase), membrane-bound enzymes (Na+/K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase), and antioxidant biomarkers (reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). Overall, MHC at 200 mg/kg bw dose significantly (p ≤ 0.05) sheltered the red blood cells from the assault of free radicals, stabilized the structural and functional integrity of hepatocytes, hindered acetaminophen (APAP) biotransformation to its toxic metabolites, and endorsed conjugating abilities to detoxify toxic entities. Furthermore, MHC significantly (p ≤ 0.05) activated enzymatic machinery to scavenge/inhibit the formation of reactive oxygen species, regulated nucleic acid metabolism, surface potential, and membrane fluidity, attenuated tissue breakdown, quenched peroxyl radicals, and provided protection against tissue injury. The necroinflammatory scores revealed strong evidence of MHC (200 mg/kg bw) effectiveness against the paracetamol-induced hepatotoxicity in rats at p ≤ 0.05. The synergistic effect of major inherent phytoconstituents (kaempferol, ellagic acid, and gallic acid), detected by HPLC-PDA, in MHC might have overturned the paracetamol-induced biochemical toxic alterations in rat liver.
Asunto(s)
Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas , Extractos Vegetales/uso terapéutico , Acetaminofén/toxicidad , Animales , Antioxidantes/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Femenino , Peroxidación de Lípido , Hígado/efectos de los fármacos , Hígado/metabolismo , Estrés Oxidativo , Ratas , Ratas WistarRESUMEN
BACKGROUND: The present study was carried out to prepare multi-herbal combination via comparing antioxidant activity and polyphenolic composition of five medicinal plant extracts of Punica granatum L., Putranjiva roxburghii Wall., Swertia chirata Buch.-Ham., Tinospora cordifolia (Willd.) Miers and Trigonella corniculata L. METHODS: The herbs were individually evaluated using in vitro antioxidant assays and analyzed by HPLC-PDA. The resultant data was examined using principal component analysis (PCA). Further, herbal combination was prepared on the basis of PCA. RESULTS: The PCA divided the plants into three groups. The leading or primary group contained P. granatum and P. roxburghii with the highest antioxidant activity strongly correlated with high amount of kaempferol. S. chirata was acknowledged as nourisher herb in one and T. cordifolia and T. corniculata were identified as stimulator herbs in other group. The herbal combination exhibited high antioxidant activity as compared to the individual plants. The combination revealed good antiproliferative efficacy against hepatocellular carcinoma (HepG2) cells with IC50 of 75.864 µg/ml. CONCLUSIONS: The activity observed in vitro with HepG2 cells suggests that the herbal combination can provide therapeutic activity in vivo in future. The study may provide information regarding precise preparation of multi-herbal formulations using PCA as a tool in pharmaceutical industries.
Asunto(s)
Antioxidantes/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Compuestos de Bifenilo/química , Proliferación Celular/efectos de los fármacos , Células Hep G2 , Humanos , Límite de Detección , Estrés Oxidativo/efectos de los fármacos , Picratos/química , Análisis de Componente PrincipalRESUMEN
Cancer cell lines of human tissue origin have been extensively used to investigate antiproliferative activity and toxicity of herbal extracts, isolated compounds, and anticancer drugs. These cell lines are genetically and/or epigenetically well characterized to determine the altered expression of proteins within given cellular pathways and critical genes in cancer. Human derived hepatoma (HepG2) cell line has been extensively exploited to examine cytoprotective, antioxidative, hepatoprotective, anti-hepatoma, hypocholesterolemic, anti-steatosis, bioenergetic homeostatic and anti-insulin resistant properties. Moreover, mechanism of action of various botanicals and bioactive constituents has been reported using these cells. HepG2 cells have significant differences as compared to primary hepatocytes with respect to expression of cytochrome P450 enzymes and xenobiotic receptors in conventional in vitro culture conditions. Therefore, strategies have been employed to overcome limitations of two dimensional (2D) in vitro HepG2 cell culture in order to recognize functional biomarkers more accurately and to boost its predictive value in clinical research. In consequence, three dimensional (3D) human hepatoma cell culture models are being developed as a resource to achieve these goals of simulating the in vivo tumor microenvironment. It is assumed that bioengineered 3D hepatoma cell culture models can provide significant assistance in scrutinizing the molecular response of herbal natural products to recognize novel prognostic targets and crucial biomarkers in treatment strategies for cancer patients in near future.
Asunto(s)
Bioingeniería , Biomarcadores , Células Hep G2 , Modelos Biológicos , Extractos Vegetales/farmacología , Biomarcadores/análisis , Biomarcadores/química , Biotecnología , Evaluación Preclínica de Medicamentos , Células Hep G2/citología , Células Hep G2/efectos de los fármacos , Células Hep G2/metabolismo , HumanosRESUMEN
Natural products are of great surge in the identification of chemopreventive agents and biologically active molecules for the development of new promising therapeutic agents. These agents influence the cascade of biochemical and molecular signalling pathways involved in numerous physiological and pathological processes. The natural agents combat the dogma associated with the most dreaded, unconquered health concern and a multigenic disease- cancer. A category of plants known as adaptogens maintain perturbed homoeostasis, augment adaptations to noxious stimuli (exposure to cold, heat, pain, general stress, infectious organisms) and offer endurance to attenuate several disorders in human beings. The well known adaptogens and immunomodulators such as Rhodiola rosea, Withania somnifera, Tinospora cordifolia, Bacopa monnieri, Emblica officinalis, Glycyrrhiza glabra, Asparagus racemosus, Ocimum sanctum and Panax notoginseng claimed to have significant antioxidant and anticarcinogenic properties due to the presence of various biologically active chemical compounds. Their immunopotentiating activity is mediated through the modulation of T-cell immunity biochemical factors, transcription factors, some genes and factors associated with tumor development and progression. The combinatory formulation of active immunostimulating constituents from these plants may provide better homeostasis. These immunostimulant factors suggest their potential therapeutic significance in adjuvant or supportive therapy in cancer treatment.
Asunto(s)
Factores Inmunológicos/farmacología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Adaptación Fisiológica/efectos de los fármacos , Animales , Anticarcinógenos/aislamiento & purificación , Anticarcinógenos/farmacología , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Humanos , Factores Inmunológicos/aislamiento & purificación , Transducción de Señal/efectos de los fármacos , Estrés Fisiológico/efectos de los fármacosRESUMEN
The toxicity induced by 7, 12-dimethylbenz(α)anthracene (DMBA) has been widely delineated by a number of researchers. This potent chemical damages many internal organs including liver, by inducing the production of reactive oxygen species, DNA-adduct formation and affecting the activities of phase I, II, antioxidant and serum enzymes. Glucosinolate hydrolytic products like isothiocyanates (ITCs) are well known for inhibiting the DNA-adduct formation and modulating phase I, II enzymes. Sulforaphane is ITC, currently under phase trials, is readily metabolized and inter-converted into erucin upon ingestion. We isolated erucin from Eruca sativa (Mill.) Thell. evaluated its hepatoprotective role in DMBA induced toxicity in male wistar rats. The rats were subjected to hepatic damage by five day regular intraperitoneal doses of DMBA. At the end of the protocol, the rats were euthanized, their blood was collected and livers were processed. The liver homogenate was analyzed for phase I (NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, cytochrome P450, cytochrome P420 and cytochrome b5), phase II (DT diaphorase, glutathione-S-transferase and γ-glutamyl transpeptidase) and antioxidant enzymes (superoxide dismutase, catalase, guaiacol peroxidise, ascorbate peroxidise, glutathione reductase and lactate dehydrogenase). The level of thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes and reduced glutathione in the liver homogenate was also analyzed. The serum was also analyzed for markers indicating hepatic damage (alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, direct bilirubin and total bilirubin). Erucin provided significant protection against DMBA induced damage by modulating the phase I, II and antioxidant enzymes. The histological evaluation of liver tissue was also conducted, which showed the hepatoprotective role of erucin.