Cassia auriculata L. (Caesalpiniaceae) is a herb, used as a traditional Indian medicine for inflammation and rheumatism and it is reported to have anti-inflammatory and analgesic activity. In view of its potent anti-inflammatory activity, the present study was designed to evaluate its anti-arthritic activity and to identify the phytoconstituents responsible for the proposed activity. Anti-arthritic activity of ethyl acetate fraction of Cassia auriculata leaves (EACA) was evaluated using Freund's complete adjuvants (FCA) induced arthritic models in wistar rats. Arthritic assessment was carried out on basis of parameters including paw oedema, motor incordination and nociceptive threshold. At the end of study period, animals were sacrificed and various biochemical, oxidative stress, haematological, radiological and histological parameters were evaluated. The ethyl acetate fraction of Cassia auriculata leaves (EACA) was subjected to qualitative and quantitative phytochemical investigation along with HPTLC analysis using standard biomarker quercetin and gallic acid. Administration of EACA significantly attenuated the behavioural, biochemical, haematological, radiological alteration induced by the FCA in dose dependent manner. Tibiotarsal joint was extracted for histopathology. The overall results indicate that EACA exerts potent protective effect against FCA induced arthritic rats which is due to its major phytoconstituents quercetin and gallic acid. From our study we can come to a conclusion that the quercetin and gallic acid present in EACA possess promising ant-arthritic activity by modulating bone erosion which may be attributed to its anti-inflammatory and analgesic activity.
Gonadotropin-primed immature rats (GPIR) were used to study the anti-ovulatory effect of 4-(4-hydroxy-3-methyl-hex-5-enyl)-chroman-2,7-diol (chroman derivative) isolated from seeds of Ensete superbum on ovulation. Present results depicted dose-related anti-ovulatory effect of the chroman derivative at 2mg/kg bw and 4mg/kg bw. Chroman derivative showed dose-dependent anti-estrogenic activity on MCF-7 cell line. Attenuation of ovulation was associated with a lowered ovarian estrogen and progesterone levels along with reduced levels of some major cytokines, i.e. TNFα, VEGF, IL-6 and IL-1β, indicating the disrupted cytokinine signaling. Unruptured preovulatory follicles were found in all the ovaries extracted from animals treated with chroman derivative. Our findings demonstrated that chroman derivative has potential contraceptive activity through its anti-estrogenic activity which leads to inhibition in ovulation and attenuated ovarian cytokinine signaling.
The heart is a major target organ for thyroid hormone action and marked changes occur in cardiac function in the case of hypo- or hyperthyroidism. Hyperthyroidism is a common metabolic disorder with prominent cardiovascular manifestation. We studied the changes in the heart structure and functions of hyperthyroid rat and ameliorating and protective role of ascorbic acid in treatment. Fourty male albino rats were equally divided into five groups; the first and second groups were the control and ascorbic acid groups respectively. Third group was the hyperthyroid rat group while 4th and 5th groups were co- and post-treated hyperthyroid rat with ascorbic acid respectively. Serum T3 and T4 levels were significantly increased also; TSH levels were significantly decreased in hyperthyroid rat as compared to control rat groups. Cholesterol, triglyceride, LDL-c and VLDL-c were significantly decreased when compared with control group. Many of abnormalities as severe hydrophobic changes of myofibrillar structure with striations, hypertrophy, cytoplasmic vacuoles and marked increase in desmin immunoreactivity were observed in left ventricle in hyperthyroid rats. Treatment with ascorbic acid helps in improving the adverse effect of hypothyroidism and also the histopathological and desmin immunoreactivity results confirms this finding.
Rheumatoid arthritis is a systemic inflammatory disease, which mainly affects joints but can also affect other organs. Ocimum gratissimum L. (Lamiaceae) is a herb, which is reported to have anti-inflammatory activity. So the present investigation was designed to evaluate antiarthritic potential of O. gratissimum in Collagen induced arthritis (CIA) in laboratory animals. Fresh leaves were extracted using 95% ethanol by maceration process. The extracts were tested against collagen induced female Sprague-Dawley rats. Arthritis assessment was carried out on the basis of parameters including arthritic score, body weight and paw volume. On day 41, animals were evaluated for biochemical parameter, radiological parameter and histological parameters. Treatment with 500 mg/kg of EEOG significantly reduced arthritic score, paw volume and almost restored body weight of arthritic animals compared to control animals. Meanwhile, the treatment significantly attenuated biochemical, radiological and histopathological alteration induced by CIA. EEOG can able to nullify most of the ill effects produced by CIA in rats. However, further studies are needed to carry out identification, isolation of active fractions of EEOG to unravel the mechanism of drug.
Lambda cyhalothrin (LTC) is a synthetic pyrethroid insecticide, widely used to control insect pests in agriculture, public health, and homes and gardens. In the present study, an attempt has been made to study the effect of lambda cyhalothrin on biochemical, hematological parameters and ameliorating effects of palm dates (Phoenix dactylifera) in male wistar rat. Adult male Wistar rats were divided into four different groups. Group I served as control; group II received lambda cyhalothrin at a dose of 8mg/kg (1/10 LD50) dissolved in water for 21 days orally; group III received P. dactylifera (200mg/kg BW for 21 days) orally; group IV P. dactylifera alone treated. LTC-induced liver toxicity was measured by the increased activities of serum hepatic marker enzymes like aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, along with increased elevation of lipid peroxidation and reduction in the levels of enzymic and non-enzymic antioxidants levels. Lambda cyhalothrin exposure leads to adverse effects on hematological parameters including erythrocyte (RBCs) and leukocyte (WBCs) counts, hemoglobin concentration (Hb), hematocrit (Hct) and blood indices (MCV and MCH). However, treatment with P. dactylifera normalized the levels of hepatic markers, antioxidant and non-enzymic antioxidant, lipid peroxidation products and all the hematological parameters. These findings highlight the efficacy of P. dactylifera as protective effects against lambda cyhalothrin induced toxicity.
Sun continuously emits UV radiation which produces series of pathological changes in the body, in long term, this ultimately results in photoaging and skin cancer on long term. Repeated UV exposure increases oxidative stress, nitrosative stress and inflammatory mediators which lead to activation of p38, MMPs and results in photoaging. Lycopene is an antioxidant and very low dose of dexamethasone provides anti-inflammatory effect. Animals were applied with lycopene gel, dexamethasone gel and combination of dexamethasone and lycopene gel after exposing to UV radiation. After experimentation period effectiveness, of treatment were evaluated by morphological, biochemical and histopathological parameters. The animals which had received lycopene and standard treatment showed less wrinkles in comparison to UV irradiated and dexamethasone treated group. Lycopene treatment decreased the TBARS level from 51.2±2.417% to 23.593±3.945%, increased by chronic UV radiation. Similarly, collagen, catalase and GSH level was increased from 56.12±2.626% damage to 20.56±2.029%, 64.59±1.743% damage to 19.507±4.997% and 48.780±1.682% reduction to 21.927±7.248%. Histopathological study and epidermal thickness parameter also revealed that lycopene provide protection against UV radiation. In case of dexamethasone treatment, either alone or in combination did not provide significant (P<0.001) protection, which may be due to its inherent property to generate oxidative stress in mice. It is noteworthy to report that lycopene provide protection against photoaging by virtue of antioxidant property.
Thalidomide is one of the anti-angiogenic drugs, which have been investigated as a possible treatment for various cancers and diseases. This work aimed to study novel thalidomide analogs for their anti-cytotoxicity, anti-angiogenic, treratogenic gene (FGF-2) expression as well as changes in histone deacetylase (HDAC) activity and nuclear factor kappa-B (NF-κB) level using two different cancer cell lines (Hep-G2 and MCF-7 cells). MTT assay was used to assess the cytotoxic effect of thalidomide analogs against Hep-G2 and MCF-7 cells. HDAC activity was estimated by colorimetric assay. NFκB- P65, pro-angiogenesis and anti-angiogenesis markers were determined by Enzyme-linked immunosorbent assay (ELISA). FGF-2 expression was confirmed by reverse transcription-polymerase chain reaction (RT-PCR). Thalidomide dithiocarbamate analogs 1, 5 and thalidomide dithioate analog 3 showed elevation in their cytotoxic activity better than thalidomide. Thalidomide dithioate analog 2 and thalidomide dithiocarbamate analog 4 showed reduction in pro-angiogenic and elevation of anti-angiogenic factors in both cell lines; furthermore, analog 1 is the most potent analog in MCF-7 cells as an anti-angiogenic agent. In Hep-G2 cells, analogs 1, 2, 4 showed a significant increase while analogs 3 and 5 induced a significant decrease in NF-κB level in relation to thalidomide. A drastic decline in HDAC activity was demonstrated in the following order 2>thalidomide>1>3>5>4 of the control activity. In conclusion, this study showed that thalidomide analogs are more potent anti-tumor agents with more pronounced effect by working selectively on specific types of tumors than thalidomide.
Herbal medicines are gaining growing interest because of their cost- effective, eco- friendly attributes and true relief from disease condition. Sarcostemma acidum was documented in many folklore practices for various psychiatric conditions. It has been dealt with in detail in “SHRUSHRUTHA SAMHITHA”. Ethyl Acetate Extract of the whole plant Sarcostemma acidum (EASA) was evaluated for psychopharmacological effects, Anti Psychotic, Anxiolytic and CNS inhibitory activity. Anti psychotic effects of EASA was assessed by Condition Avoidance Response and cataleptic Scoring test using pole climbing and Bar test respectively. Elevated Plus maze (EPM) and Hole Board Apparatus (HBA) was employed for the anxiolytic activity while Actophotometer was used to assess the CNS inhibitory activity. EASA (650mg/kg), Haloperidol (5mg/kg) and 1% CMC was administered to the test, standard and control group respectively for Antipsychotic activity, while For Anxiolytic and CNS depressant studies test, standard and control group receive EASA (650mg/kg), Diazepam (2mg/kg) and 1% CMC respectively. It was found that EASA significantly enhance the latency period to climb the pole and the cataleptic score which indicates its suppression on CAR activity, which clearly confirms its Anti Psychotic activity, might be due to blockade of dopaminergic pathway. It was observed that EASA at a dose of 650mg/kg significantly increases the no: of entries in to the open arm in EPM as well as no: of head poking in HBA, which reflects its increase in exploratory behaviour which indicates the anxiolytic activity. Reduction in the loco motor activity in actophotometer indicates CNS depressant property of the drug.
This study investigated the effect of N-acetylcysteine (NAC) against γ-radiation-induced cytotoxicity in human hepatocellular carcinoma (HepG2) cells. HepG2 Cells were incubated with 20mM of NAC for 24h prior to 6Gy γ-irradiation. Apoptosis markers, such as caspase-3 and DNA fragmentation and oxidative stress markers, such as total nitrate/nitrite (NO(x)) and malondialdehyde (MDA) levels, superoxide dismutase (SOD) and glutathione (GSH) content were studied. Half of the lethal dose (LD50) of NAC on HepG2 cell viability was found to be 20mM/mL after incubation for 48h. Incubation of irradiated HepG2 cells with NAC inhibited γ-radiation-induced increases in caspase-3 activity and DNA fragmentation. Treatment with NAC before γ-radiation restored the changes induced by γ-irradiation by increasing SOD activity and GSH content in parallel with a decrease in MDA and NO(x) levels in HepG2 cells. NAC has a modulatory effect against γ-radiation-induced oxidative damage plausibly ascribable to its antioxidant/free radical scavenging ability.
The widespread use of organophosphorus insecticides (OPIs) consequently leads to the exposure of manufacturing workers, field applicators, the ecosystem, and finally the public to the possible toxic effects of OPIs. In addition, drugs or pharmaceutical products, which are used to cure diseases, are also xenobiotics with both therapeutic/toxic potentials. It is evident from the literature, which is very limited, that drug/insecticide interactions can result in altered response/toxicity, which is of clinical relevance. The aim of the present study was designed to assess the adverse effects of exposure to aspirin and diazinon and their combination on liver of male rats and hepatoprotective potential of selenium (Se). Rats were oral administered with vehicle, acetyl salicylic acid (ASA) at the maximum administration dose (1350 mg/personal/day = 22.5 mg/kg. b.wt.), diazinon (DIA) at 20 mg/kg. b.wt. and Se at a dose of 200 μg/kg b.wt./day and their combinations for 28 consecutive days. Serum liver biomarkers, e.g. ALT&AST, ALP, ChE, LDH, albumin, total protein were determined as well as histological and histochemical studies. Body weight was statistically (P ≤ 0.05) decreased, while relative liver weight was statistically (P ≤ 0.05) increased in DIA and ASA + DIA-treated groups. The activities of serum aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were statistically (P ≤ 0.05) increased, while the activity of cholinesterase (ChE) was decreased in rats exposed to DIA, ASA and DIA + ASA. In addition, administration of DIA, ASA and their combination resulted in damage of liver structures and increase in the immunoreactivity of caspase-3 expression in the cytoplasm of the hepatocytes as compared to the control group. Combination therapy with Se significantly (P ≤ 0.05) restored these alterations to within the normal limits and prevents disruptions of liver structures. The present study indicates that liver enzymes, histopathology and immunoreactivity of caspase-3 would trigger ASA- and DIA-induced liver injury. The severities of such observations were more pronounced in their combined exposure. Combination therapy with Se restored these alterations to within the normal limits and prevents disruptions of liver structures. The data throw light on the problem of simultaneous exposure to OPIs and commonly used drugs especially that are metabolised by CYP450. Accordingly, ASA should be avoided since many of the adverse effects associated with these drugs are similar to the complications of chronic liver disease especially of agricultural workers in developing countries, where the handling of drugs without medical prescription. We suppose that antioxidant supplementation may be beneficial for the people using ASA for longer periods.
Parkinson disease is a progressive neurodegenerative disorder characterized by the presence of Lewy bodies with dense α-synuclein self-aggregation which is responsible for its toxic effect on Substantia nigra pars compacta and resultant neuronal death. Hence, blocking alpha-synuclein aggregation is a new channel to cure PD. This study initially investigates drug likeness and ADMET properties of CNB-001, 7,8 dihydroxyflavone, curcumin, naringenin and emodin and its inhibitory effect on alpha-synuclein (PDB: 1XQ8) aggregation via molecular docking (LeadIT). Results revealed that the ligands satisfy drug likeness and ADMET properties and best-fit ligands were associated with VAL95, GLU83 and ALA91 as major amino acid residues of receptor site. Moreover, CNB-001 showed potent inhibitory effect than other compounds with a docking score of –13.6158. Further, we investigated the inhibitory effect of CNB-001 against alpha-synuclein expression using MPTP induced Parkinson mice model. Results explicated and confirmed that CNB-001 inhibited α-synuclein expression significantly when compared to MPTP group as evinced by western blotting. Therefore, these results attribute that CNB-001 can be further developed as a promising therapeutic candidate for PD treatment.
Cancer is a group of disease characterized by uncontrolled cell divisions leading to abnormal growth of the tissue. Worldwide, breast cancer is the second most common type of cancer after lung cancer. Estrogen and progesterone bind to the receptors and may work with growth factors to cause cancer cell growth and proliferation. Estrogen receptor alpha (ERα) is essential for mammary gland development and also plays a central role in breast cancer development by mediating estrogen induced cell proliferation. Multidisciplinary scientific investigations are making best efforts to combat this disease, but the perfect cure is yet to be achieved. The side effects of the available drugs make the need for the necessity of new improved drugs. Cyanobacterial resource offers a great scope for discovery of new drugs for breast cancer. Cyanobacterial novel bioactive compounds with unique biological activities may be useful in finding the potential drugs with greater efficacy, specificity for the treatment of human diseases. Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. Nowadays, molecular docking approaches are routinely used in modern drug design to understand drug–receptor interaction. Computational techniques can strongly support and help the design of novel, more potent inhibitors by revealing the mechanism of drug-receptor interaction. Hence, the present study is interested to evaluate the interaction of the selected ligands with the breast cancer target receptor. From the study it is concluded that Cryptophycin F, a bioactive compound produced by the Nostoc is a promising potential drug for breast cancer.
Hepatocellular carcinoma is the leading cause of death and its incidence is rising year by year. There are numerous antioxidants available in various sources, including microorganisms. We had an attempt on validating the effect of diazepinomicin from Micromonospora strain against human hepatoma cell line (HepG2). Trypan blue exclusion assay was performed to determine the dead cells. Propidium iodide and Hoechst staining was performed to determine the apoptotic bodies. DNA fragmentation was performed on agarose gel electrophoresis and the expression of BAX and Bcl2 proteins were determined. Trypan blue exclusion assay showed dose-dependent cell death. Propidium iodide and Hoechst staining showed apoptotic bodies. DNA fragments were seen in both diazepinomicin 10 and 15μM/mL treated Hep G2 cells. Western blot assay showed low intensity bands in diazepinomicin 10 and 15μM/mL treated Hep G2 cells. Thus, the downregulation of these protein expressions reveal that the diazepinomicin has the ability to induce apoptosis. From all the parameters, it could be concluded that the diazepinomicin has anticancer potency against human hepatoma cell line (HepG2).
Syringic acid (SA) is a naturally occurring O-methylated trihydroxybenzoic acid present in wine and released as a breakdown product of malvidin, a primary plant pigment (an anthocyanidin). In this study, the neuroprotective efficacy of syringic acid (SA) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probencid (MPTP/p) induced mouse model of PD was investigated. The C57BL/6 mice were given 10 doses of MPTP/p for five consecutive weeks with 3.5day interval. Administration of MPTP/p led to reduced motor coordination, neurochemicals and tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter-2 (VMAT2) expression. In addition, increased oxidative stress markers and the expression of inflammatory markers, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2). Pre-oral treatment with SA (20mg/kg) was found to improve the MPTP/p-induced impaired motor functions by restoring the catecholamine content and antioxidant enzymes level. In addition, it ameliorated the expressions of TH, DAT and VMAT2 and also significantly attenuated MPTP/p-induced increased inflammatory markers expressions. These results partially explain the pharmacological efficacy of SA as a potential therapeutic agent for the treatment of MPTP/p-induced mice model of PD, together with its neuroprotective effect and reduce the progression of PD.
The key initiating process in atherogenesis is the subendothelial retention of apolipoprotein B-containing lipoproteins. Retained lipoproteins are chemically and enzymatically modified, inducing a chronic inflammatory response. Therapeutic approaches for atherosclerosis treatment have been focused on the control of risk factors, such as hypercholesterolemia, hypertension, and diabetes mellitus. Nonetheless, the efficacy of these strategies is limited and unfortunately the health problem persists. On the other hand, development of therapies targeting the interactions between low-density lipoproteins and components of the extracellular matrix has been poorly addressed. In this work, we review the response-to-retention hypothesis and the recent data on therapeutic approaches targeting the retentive process of proatherogenic low-density lipoproteins.
Epilepsy is a complex neurological disorder affecting 50 million of world's total population. Number of medicinal plants has been used to treat the convulsion. In ancient time Morus alba was used to treat epilepsy and mental illness. In Chinese medicine also M. alba is used as neuroprotective herbs. The present study was designed to explore the effect of Morusin, a flavonoid glycoside isolated from M. alba as anticonvulsant activity along with biochemical mechanism. Morusin was isolated from M. alba and acute toxicity study was determined. Anticonvulsant activity of Morusin (5 and 10 mg/kg, i.p.) was studied by using isoniazid (INH) and maximal electroshock (MES)-induced convulsion models; diazepam (5 mg/kg) and phenytoin (20 mg/kg) were used as standards, respectively. Biochemical mechanism was investigated by estimating the GABA level in brain. The median lethal dose (LD50) of Morusin was found up to 20 mg/kg. Treatment with Morusin (5 and 10 mg/kg) delayed onset of convulsion and tonic hind limb extension along with duration of tonic-clonic convulsions as well as it significantly reduced mortality in INH and MES-induced convulsion. Rats treated with Morusin (5 and 10 mg/kg) significantly increased level of brain GABA at both doses. The findings of current study provide pharmacological credibility to anticonvulsant activity of Morusin. The protection against the convulsions and restoration of GABA level give a suggestion to its probable mechanism of action.
The chemokine CXCL12 (SDF-1) is an extracellular chemokine which binds to its cell surface receptor CXCR4. The axis of CXCL12/CXCR4 has been considered to play an important role for cancer cell migration. Recently, the aberrant expression of CXCR4 has been found during the malignancy of colorectal cancer (CRC), where it plays a crucial role in, among others, the proliferation, angiogenesis and metastatic spread. Various intracellular signal transduction cascades and effectors related to the CXCR4/CXCL12 axis have been determined, such as MAPK, PI-3K/Akt and Wnt. Currently, the potential role of CXCR4/CXCL12 as the therapeutic target for treatment of CRC has been focused. In this review, we summarized recent research on CXCL12/CXCR4 axis in the development of CRC.
The recognition of emotions from facial expressions is a basic human aptitude. The aging process is related with a decrease of this ability, particularly in the recognition of negative emotions. This decrease is more prominent in the context of dementia. Despite the growing of researches on emotion recognition, there is a lack of instruments capable of identifying individual differences regarding aging and dementia. This work aims to determine the psychometric properties of a facial emotion recognition task (Gandra-BARTA). The sample is composed by three groups: Young Adults (YA) group (n=12); Old Adults (OA) group (n=17); Alzheimer's Disease (AD) group (n=26), made up of subjects with diagnosis of probable AD. The Gandra-BARTA showed good internal consistency. In comparison to the YA, the OA group took more time to complete Gandra-BARTA, had less correct emotional identifications and they have under-recognized facial expressions of rage and neutral emotions. On the other hand, the AD group showed worst performance on every aspect of the Gandra-BARTA when compared to the OA group, except in the identification of sadness and fear. A cutoff score of 24 correct recognitions on Gandra-BARTA differentiate OA from AD subjects with a sensibility of 100% and a specificity of 88.5%. The Gandra-BARTA revealed good internal consistency making it a reliable instrument to assess the ability to recognize emotions from facial expressions. It also proved to be sensitive to changes in aging and dementia with high discriminant validity for AD.
The present study was designed to investigate the possible association of concomitant administration of trigonelline (TRIG) and sitagliptin (SITA) on cardiomyopathy in diabetic rats. Diabetes was induced in Wistar rats by administration of nicotinamide (NICO; 110 mg/kg) and streptozotocin (STZ; 65 mg/kg) intraperitonelly (i.p.). After confirmation of diabetes, rats were divided into following groups i.e. group 1: non-diabetic rats (ND); Group 2: diabetic rats (DC); Group 3: TRIG (50 mg/kg, p.o.); Group 4: SITA (5 mg/kg, p.o.); Group 5: TRIG + SITA (50 + 5 mg/kg, p.o.). Treatment with selected dose of TRIG and SITA was started from 3rd week after NICO–STZ injection and was continued up to 11th week. Cardiomyopathy was assessed by measuring serum glucose level, enzymatic cardiac markers, electrographic abnormalities, heamodynamic changes, lipid levels and histological examination of isolated heart tissue of treated animals. NICO–STZ diabetic rats showed extensive hyperglycemia, hyperlipidemia, and elevated levels of enzymatic cardiac markers compared to non-diabetic rats. Concomitant and monotherapy treatment of TRIG and SITA exhibited significant decrease in hyperglycemia as compared to diabetic rats. Whereas TRIG + SITA considerably reduced hyperlipidemia, alteration in levels enzymatic cardiac markers and improvement in cardiac function by improved electrographic abnormalities and heamodynamic changes. Overall, the findings revealed in this investigation demonstrated that concomitant administration of TRIG + SITA can be strong pharmacological therapy as compared to monotherapy used for the treatment of hyperglycemia, hyperlipidemia and cardiac dysfunctions in NICO–STZ-induced cardiomyopathy in Wistar rats. We conclude that concomitant administration of TROG and SITA showed additive cardioprotective effect compared to monotherapy.
Time passing drives all living organismes to cellular decline with age-associated dysfuntion, diseases and death. It appeared now that ageing like any biological process is surceptible to regulation. Environmental factors such as stimuli/stresses as well as endogenous factors, i.e., expression and mutation of some particular genes might act as the main regulators. Psychological factors as a human specific dimension could contribute in delaying the senescence decline.
