Alcohol use disorder (AUD) has been associated with neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Prolonged excessive alcohol intake contributes to increased production of reactive oxygen species that triggers neuroimmune response and cellular apoptosis and necrosis via lipid peroxidation, mitochondrial, protein or DNA damage. Long term binge alcohol consumption also upregulates glutamate receptors, glucocorticoids and reduces reuptake of glutamate in the central nervous system, resulting in glutamate excitotoxicity, and eventually mitochondrial injury and cell death. In this review, we delineate the following principles in alcohol-induced neurodegeneration: (1) alcohol-induced oxidative stress, (2) neuroimmune response toward increased oxidants and lipopolysaccharide, (3) glutamate excitotoxicity and cell injury, and (4) interplay between oxidative stress, neuroimmune response and excitotoxicity leading to neurodegeneration and (5) potential chronic alcohol intake-induced development of neurodegenerative diseases, including Alzheimer's and Parkinson's disease.
The antioxidant role of sulfite reductase (SiR) derived from Arthrospira platensis (Ap) was identified through a short peptide, TL15. The study showed that the expression of ApSiR was highly expressed on day ten due to sulfur deprived stress in Ap culture. TL15 peptide exhibited strong antioxidant activity when evaluated using antioxidant assays in a concentration ranging from 7.8 and 125 μM. Further, the cytotoxicity of TL15 peptide was investigated, even at the higher concentration (250 μM), TL15 did not exhibit any toxicity, when tested in vitro using human leucocytes. Moreover, a potential reduction in reactive oxygen species (ROS) production was observed due to the treatment of TL15 peptide (>15.6 μM) to H2O2 exposed leucocytes. For the in vivo assessment of TL15 toxicity and antioxidant ability, experiments were performed in zebrafish (Danio rerio) larvae to analyse the developmental toxicity of TL15 peptide. Results showed that, exposure to TL15 peptide in tested concentrations ranging from 10, 20, 40, and 80 μM, did not affect the development and physiological parameters of the zebrafish embryo/larvae such as morphology, survival, hatching and heart rate. Fluorescent assay was performed using DCFH-DA (2,7-dichlorodihydrofluorescein diacetate) to examine the production of intracellular reactive oxygen species (ROS) in zebrafish treated with TL15 peptide during the embryo-larval stages. Fluorescent images showed that pre-treatment with TL15 peptide to attenuate the H2O2 induced ROS levels in the zebrafish larvae in a dose-dependent manner. Further to uncover the underlying biochemical and antioxidant mechanism, the enzyme activity of superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPO) levels were studied in zebrafish larvae. TL15 pre-treated groups showed enhanced antioxidant enzyme activity, while the hydrogen peroxide (H2O2) exposed larvae showed significantly diminished activity. Overall results from the study revealed that, TL15 act as a potential antioxidant molecule with dose-specific antioxidant property. Thus, TL15 peptide could be an effective and promising source for biopharmaceutical applications.
Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of characteristic psychiatric disturbances and cognitive and motor dysfunction. To the best of our knowledge, there is no treatment available to completely mitigate the progression of HD. Among various therapeutic approaches, exhaustive literature reports have confirmed the medicinal benefits of natural products in HD experimental models. Building on this information, this review presents a brief overview of the neuroprotective mechanism(s) of natural products against in vitro/in vivo models of HD. Relevant studies were identified from several scientific databases, including PubMed, ScienceDirect, Scopus, and Google Scholar. After screening through literature from 2005 to the present, a total of 14 medicinal plant species and 30 naturally isolated compounds investigated against HD based on either in vitro or in vivo models were included in the present review. Behavioral outcomes in the HD in vivo model showed that natural compounds significantly attenuated 3-nitropropionic acid (3-NP) induced memory loss and motor incoordination. The biochemical alteration has been markedly alleviated with reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and increased mitochondrial energy production. Interestingly, following treatment with certain natural products, 3-NP-induced damage in the striatum was ameliorated, as seen histologically. Overall, natural products afforded varying degrees of neuroprotection in preclinical studies of HD via antioxidant and anti-inflammatory properties, preservation of mitochondrial function, inhibition of apoptosis, and induction of autophagy.
Background:Gynura species have been used traditionally to treat various ailments, such as fever, pain, and to control blood glucose level. This systematic review critically discusses studies regarding Gynura species that exhibited antioxidant and anti-inflammatory effects, thus providing perspectives and instructions for future research of the plants as a potential source of new dietary supplements or medicinal agents. Methods: A literature search from internet databases of PubMed, Scopus, Science Direct, e-theses Online Service, and ProQuest was carried out using a combination of keywords such as "Gynura," "antioxidant," "anti-inflammatory," or other related words. Research articles were included in this study if they were experimental (in vitro and in vivo) or clinical studies on the antioxidant or anti-inflammatory effects of Gynura species and if they were articles published in English. Results: Altogether, 27 studies on antioxidant and anti-inflammatory effects of Gynura species were selected. The antioxidant effects of Gynura species were manifested by inhibition of reactive oxygen species production and lipid peroxidation, modulation of glutathione-related parameters, and enzymatic antioxidant production or activities. The anti-inflammatory effects of Gynura species were through the modulation of inflammatory cytokine production, inhibition of prostaglandin E2 and nitric oxide production, cellular inflammatory-related parameters, and inflammation in animal models. The potential anti-inflammatory signaling pathways modulated by Gynura species are glycogen synthase kinase-3, nuclear factor erythroid 2-related factor 2, PPARγ, MAPK, NF-κB, and PI3K/Akt. However, most reports on antioxidant and anti-inflammatory effects of the plants were on crude extracts, and the chemical constituents contributing to bioactivities were not clearly understood. There is a variation in quality of studies in terms of design, conduct, and interpretation, and in-depth studies on the underlying mechanisms involved in antioxidant and anti-inflammatory effects of the plants are in demand. Moreover, there is limited clinical study on antioxidant and anti-inflammatory effects of Gynura species. Conclusion: This review highlighted antioxidant and anti-inflammatory effects of genus Gynura and supported their traditional uses to treat oxidative stress and inflammatory-related diseases. This review is expected to catalyze further studies on genus Gynura. However, extensive preclinical data need to be generated from toxicity and pharmacokinetic studies before clinical studies can be pursued for their development into clinical medicines to treat oxidative stress and inflammatory conditions.
Dabai pulp oil (DPO) is new oil extracted from the pulp of Canarium odontophyllum. The quality and efficacy of DPO are needed to promote its potential as a new alternative fat. Therefore, we investigate the quality of DPO, which includes moisture and volatile content (MVC), free fatty acid content (FFA), iodine value (IV), and peroxide value (PV). Furthermore, we evaluate the efficacy of DPO against hypercholesterolemia elicited by a high-cholesterol diet in rats. The MVC of DPO was <0.001 ± 0.00%. Next, the FFA in DPO was 2.57 ± 0.03%, and the IV of DPO was 53.74 ± 0.08 g iodine/100 g oil. Meanwhile, the PV of DPO was 4.97 ± 0.00 mEq/kg. Supplementation of DPO in hypercholesterolemic rats for 30 days revealed the hypocholesterolemic effect (significant reduction of total cholesterol, triglyceride, and 3-hydroxy-3-methylglutaryl-CoA reductase) accompanied by a significant reduction of inflammatory markers (C-reactive protein, interleukin-6 and tumour necrosis factor-α), and lipid peroxidation (MDA). We also observed a significant improvement of lipoprotein lipase (LPL) and antioxidant capacities (total antioxidant status, superoxide dismutase, glutathione peroxidase, and catalase) of the rats. The results on the quality and efficacy of locally made DPO suggest its potential use as a healthy alternative fat in the future.
This study reports the antioxidant property and molecular mechanism of a tryptophan-tagged peptide derived from a teleost fish Channa striatus of serine threonine-protein kinase (STPK). The peptide was tagged with tryptophan to enhance the antioxidant property of STPK and named as IW13. The antioxidant activity of IW13 peptide was investigated using in vitro methods such as DPPH, ABTS, superoxide anion radical scavenging and hydrogen peroxide scavenging assay. Furthermore, to investigate the toxicity and dose response of IW13 peptide on antioxidant defence in vitro, L6 myotubes were induced with generic oxidative stress due to exposure of hydrogen peroxide (H2O2). IW13 peptide exposure was found to be non-cytotoxic to L6 cells in the tested concentration (10, 20, 30, 40 and 50 μM). Also, the pre-treatment of IW13 peptide decreased the lipid peroxidation level and increased glutathione enzyme activity. IW13 peptide treatment upregulated the antioxidant enzyme genes: GPx (glutathione peroxidase), GST (glutathione S transferase) and GCS (glutamine cysteine synthase), in vitro in L6 myotubes and in vivo in zebrafish larvae against the H2O2-induced oxidative stress. The results demonstrated that IW13 renders protection against the H2O2-induced oxidative stress through a cellular antioxidant defence mechanism by upregulating the gene expression, thus enhancing the antioxidant activity in the cellular or organismal level. The findings exhibited that the tryptophan-tagged IW13 peptide from STPK of C. striatus could be a promising candidate for the treatment of oxidative stress-associated diseases.
The effects of medium strategies [maintenance (M), intermediary (G), and production (P) medium] on cell growth, anthraquinone (AQ) production, hydrogen peroxide (H2O2) level, lipid peroxidation, and antioxidant vitamins in Morinda elliptica cell suspension cultures were investigated. These were compared with third-stage leaf and 1-month-old callus culture. With P medium strategy, cell growth at 49 g l(-1), intracellular AQ content at 42 mg g(-1) DW, and H2O2 level at 9 micromol g(-1) FW medium were the highest as compared to the others. However, the extent of lipid peroxidation at 40.4 nmol g(-1) FW and total carotenoids at 13.3 mg g(-1) FW for cultures in P medium were comparable to that in the leaf, which had registered sevenfold lower AQ and 2.2-fold lower H2O2 levels. Vitamin C content at 30-120 microg g(-1) FW in all culture systems was almost half the leaf content. On the other hand, vitamin E content was around 400-500 microg g(-1) FW in 7-day-old cultures from all medium strategies and reduced to 50-150 microg g(-1) FW on day 14 and 21; as compared to 60 microg g(-1) FW in callus and 200 microg g(-1) FW in the leaf. This study suggests that medium strategies and cell growth phase in cell culture could influence the competition between primary and secondary metabolism, oxidative stresses and antioxidative measures. When compared with the leaf metabolism, these activities are dynamic depending on the types and availability of antioxidants.
Covalent hemoglobin binding to membranes leads to band 3 (AE1) clustering and the removal of erythrocytes from the circulation; it is also implicated in blood storage lesions. Damaged hemoglobin, with the heme being in a redox and oxygen-binding inactive hemichrome form, has been implicated as the binding species. However, previous studies used strong non-physiological oxidants. In vivo hemoglobin is constantly being oxidised to methemoglobin (ferric), with around 1% of hemoglobin being in this form at any one time. In this study we tested the ability of the natural oxidised form of hemoglobin (methemoglobin) in the presence or absence of the physiological oxidant hydrogen peroxide to initiate membrane binding. The higher the oxidation state of hemoglobin (from Fe(III) to Fe(V)) the more binding was observed, with approximately 50% of this binding requiring reactive sulphydryl groups. The hemoglobin bound was in a high molecular weight complex containing spectrin, ankyrin and band 4.2, which are common to one of the cytoskeletal nodes. Unusually, we showed that hemoglobin bound in this way was redox active and capable of ligand binding. It can initiate lipid peroxidation showing the potential to cause cell damage. In vivo oxidative stress studies using extreme endurance exercise challenges showed an increase in hemoglobin membrane binding, especially in older cells with lower levels of antioxidant enzymes. These are then targeted for destruction. We propose a model where mild oxidative stress initiates the binding of redox active hemoglobin to the membrane. The maximum lifetime of the erythrocyte is thus governed by the redox activity of the cell; from the moment of its release into the circulation the timer is set.
This study was conducted to determine the effects of increased edible palm oil consumption on community health status in the aboriginal communities in Tual Post (treatment group) and Sinderut Post (control group), Kuala Lipis, Pahang. Nutritional status, blood pressure, lipid profiles, fasting blood glucose (FBG), vitamin E (alpha-tocopherol) levels and lipid peroxidation product (malonaldehyde) levels were taken as indicators of health status. This is a pre-and post-controlled community trial in which similar variables were measured in each group. Every family of 2–6 household members was given 2–5 kg cooking palm oil per month for a period of 18 months. All subjects were measured for height (cm), weight (kg) and waist-hip ratio (WHR). For calorie intake measurement, house-to-house interviews were conducted using 24-hour dietary recall method. Blood pressure, percent body fat, lipid profiles, namely total cholesterol, high density lipoprotein cholesterol, triglyceride and fasting blood glucose (FBG) were also measured. Vitamin E (alpha-tocopherol) levels and lipid peroxidation products (MDA) were also determined. There was a significant increase (p
Introduction: Reduced cerebral blood fl ow is associated with neurodegenerative disorders and dementia, in particular. Experimental evidence has demonstrated the initiating role of chronic cerebral hypoperfusion in neuronal damage to the hippocampus, the cerebral cortex, the white matter areas and the visual system. Permanent, bilateral occlusion of the common carotid arteries of rats (two vessel occlusion - 2VO) has been introduced for the reproduction of chronic cerebral hypoperfusion as it occurs in Alzheimer’s disease and human aging. Increased generation of free radicals through lipid peroxidation can damage neuronal cell membrane. Markers of lipid peroxidation have been found to be elevated in brain tissues and body fl uids in neurodegenerative diseases, including Alzheimer’s disease, Parkinson disease and amyotrophic lateral sclerosis. Materials and Methods: Malondialdehyde (MDA), fi nal product of lipid peroxidation, was estimated by thiobarbituric acid-reactive substances (TBARS) assay kit at eight weeks after induction of 2VO in the rats and control group. Results: Our study revealed a highly signifi cant (p
Ginger extract has been reported previously by our group to exhibit anticancer and an-tioxidant effects by reducing tumour burden and lipid peroxidation respectively in he-patocarcinogenesis induced rats. The current study examined the expression of pro-apoptotic protein caspase-8 and anti-apoptotic protein Bcl-2 in hepatocarcinogenesis treated rats. Thirty normal male Wistar rats were divided into 5 groups based on the diet given: i) control (normal rat chow), ii) olive oil, iii) ginger extract (100mg/kg body weight), iv) choline deficient diet + ethionine, CDE (to induce liver cancer) and v) CDE+ ginger extract. Rats were killed at week 8, and liver tissues were excised for immuno-histochemical study to identify pro-apoptotic and anti-apoptotic proteins, caspase-8 and Bcl-2. The observation on H&E staining confirmed the CDE diet induced liver can-cer as indicated by the presence of numerous oval cells. Identification of Bcl-2 expres-sion showed that 91.6% (11/12) of the samples from the CDE group revealed positive staining while treatment with ginger extract however inhibited the expression with only 8.4% (1/12) samples showing positive staining for Bcl-2. As for caspase-8 protein, 41.7% (5/12) of the samples from CDE group showed positive staining, which in-creased to 100% (12/12) with ginger extract treatment. Our findings suggest that gin-ger extract has an anticancer effect by inducing apoptosis in liver cancer cells via up-regulation of the expression of pro-apoptotic protein, caspase-8 and down-regulation of the expression of anti-apoptotic protein Bcl-2.
Elevated glucocorticoid levels during stressed conditions have been demonstrated to impair reproductive function in rats. In our previous study investigating the dose-related effects of corticosterone (CORT) on the fertilising capacity of epididymal sperm in surgically-manipulated rats, we found that 25 mg/kg/day of CORT given subcutaneously for seven consecutive days significantly decreased the number of implantation sites and increased intrauterine embryonic loss compared to controls. Based on these findings, the current study aims to elucidate the possible mechanisms of action of CORT-induced stress on impaired sperm fertility in rats. Results of the present study showed that compared to controls, 25 mg/kg/day of CORT given subcutaneously for 7 consecutive days significantly increased the level of plasma malondialdehyde (MDA) with corresponding attenuated levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Plasma adrenocorticotropin (ACTH) and testosterone levels were also found to be decreased in CORTtreated rats. These findings suggest that CORT-induced oxidative stress and exert an inhibitory effect at the hypothalamic-pituitary-gonadal (HPG) axis, as evidenced by increased lipid peroxidation, reduced enzymatic antioxidant activities, and decreased testosterone production. These subsequently result in decreased fertilising capacity of epididymal sperm leading to poor pregnancy outcomes.
Reactive oxygen species and other radicals potentially cause oxidative damage to proteins, lipids, and DNA which may ultimately lead to various complications including mutations, carcinogenesis, neurodegeneration, cardiovascular disease, aging, and inflammatory disease. Recent reports demonstrate that Streptomyces bacteria produce metabolites with potent antioxidant activity that may be developed into therapeutic drugs to combat oxidative stress. This study shows that Streptomyces sp. MUM212 which was isolated from mangrove soil in Kuala Selangor, Malaysia, could be a potential source of antioxidants. Strain MUM212 was characterized and determined as belonging to the genus Streptomyces using 16S rRNA gene phylogenetic analysis. The MUM212 extract demonstrated significant antioxidant activity through DPPH, ABTS and superoxide radical scavenging assays and also metal-chelating activity of 22.03 ± 3.01%, 61.52 ± 3.13%, 37.47 ± 1.79%, and 41.98 ± 0.73% at 4 mg/mL, respectively. Moreover, MUM212 extract was demonstrated to inhibit lipid peroxidation up to 16.72 ± 2.64% at 4 mg/mL and restore survival of Vero cells from H2O2-induced oxidative damages. The antioxidant activities from the MUM212 extract correlated well with its total phenolic contents; and this in turn was in keeping with the gas chromatography-mass spectrometry analysis which revealed the presence of phenolic compounds that could be responsible for the antioxidant properties of the extract. Other chemical constituents detected included hydrocarbons, alcohols and cyclic dipeptides which may have contributed to the overall antioxidant capacity of MUM212 extract. As a whole, strain MUM212 seems to have potential as a promising source of novel molecules for future development of antioxidative therapeutic agents against oxidative stress-related diseases.
Oxidative stress and reactive oxygen species (ROS) constitute a major pathogenic mechanism
for the development of atherosclerosis. In the present work, the antioxidant potential of
Trihoney was investigated in hypercholesterolaemic rabbits. Thirty-six male New Zealand
white (NZW) rabbits were grouped into: normal diet (C), normal diet with 0.6 g/kg/day of
Trihoney (C+H), 1% cholesterol diet (HCD), 1% cholesterol diet with 0.3 g/kg/day of
Trihoney (HCD+H1
), 1% cholesterol diet with 0.6 g/kg/day of Trihoney (HCD+H2
), and 1%
cholesterol diet with 2 mg/kg/day of atorvastatin (HCD+At.). Animals were sacrificed following 12 weeks of treatment, and their serum was analysed for oxidised-low density lipoprotein
(Ox-LDL). Serum and aortic tissue homogenate were assayed for superoxide dismutase
(SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA). Hypercholesterolemia
caused a significant (p < 0.05) elevation in serum Ox-LDL and a significant (p < 0.05) reduction of antioxidant enzyme activities in serum of the HCD group. Trihoney induced a significant (p < 0.05) increase in antioxidant enzyme activities in serum as compared to the HCD
group. The high cholesterol diet suppressed both antioxidant enzymes in aortic homogenate.
Trihoney significantly (p < 0.05) enhanced both antioxidant enzymes in aortic homogenate.
Hypercholesterolemia induced a significant (p < 0.05) elevation of serum lipid peroxidation in
the HCD group. Trihoney caused a significant (p < 0.05) reduction of lipid peroxidation in
aortic homogenate. These results demonstrated that Trihoney has the potential to ameliorate
oxidative stress systemically, as well as locally in the atherosclerotic aorta.
Antibiotic-adjuvant combinatory therapy serves as a viable treatment option in addressing antibiotic resistance in the clinical setting. This study was carried out to assess and characterize the adjuvant potential and mode of action of linalool against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Linalool exhibited bactericidal activity alone (11,250 μg/ml) and in combination with meropenem (5,625 μg/ml). Comparative proteomic analysis showed significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in linalool-treated KPC-KP cells. Upregulation of oxidative stress regulator proteins and downregulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that linalool increases the bacterial surface charge as well as the membrane permeability. Intracellular leakage of nucleic acid and proteins was detected upon linalool treatment. Scanning and transmission electron microscopies further revealed the breakage of bacterial membrane and loss of intracellular materials. Linalool induced oxidative stress by generating reactive oxygen species (ROS) which initiates lipid peroxidation, leading to damage of the bacterial membrane. This leads to intracellular leakage, eventually killing the KPC-KP cells. Our study demonstrated that linalool possesses great potential in future clinical applications as an adjuvant along with existing antibiotics attributed to their ability in disrupting the bacterial membrane by inducing oxidative stress. This facilitates the uptake of antibiotics into the bacterial cells, enhancing bacterial killing.
The potential of Moringa oleifera Lam. (Moringaceae) and Centella asiatica (L.) Urban (Apiaceae) extracts (TGT-PRIMAAGE) in slowing the decline of memory and learning activity was investigated using D-galactose-induced ageing rat model. The extracts were profiled and standardised based on markers identified using LC/MS-QTOF. Toxicity study of the extract was done, and the rat did not show any sign of toxicity. The extract was orally administered to the rat and dose dependent (100, 500 and 1000 mg/kg) efficacy were investigated. The rats were subjected to Morris Water Maze whereby 3 parameters were studied (number of entry to platform, latency and novel object recognition). Plasma was collected for the determination of catalase (CAT) activity and levels of malondialdehyde (MDA) and advanced glycation end products (AGEs). The activity of acetylcholinesterase (AChE), level of acetylcholine (ACh) and lipid peroxidation (LPO) were measured using the brain lysates. Significant improvement (p < 0.05) was seen in the memory and learning abilities in the aged rats that received medium and high dose of TGT-PRIMAAGE, and tocotrienol. Rats treated with TGT-PRIMAAGE had also shown improved CAT activity and resulted in reduced LPO. The level of ACh was found increased in parallel with the reduced AChE activity. The capabilities of learning and memory of the TGT-PRIMAAGE treated rats were enhanced via inhibition of AChE activity and subsequently increased level of ACh.
Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance. This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate (LNA) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). LNA alone exhibited bactericidal activity at 2.5% (V/V), and in combination with meropenem (MPM) at 1.25% (V/V). Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins, indicating membrane damage in LNA-treated KPC-KP cells. Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability. Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells, inferring membrane damage. Furthermore, intracellular leakage of nucleic acid and proteins was detected upon LNA treatment. Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular materials. LNA was found to induce oxidative stress by generating reactive oxygen species (ROS) that initiate lipid peroxidation and damage the bacterial membrane. In conclusion, LNA generates ROS, initiates lipid peroxidation, and damages the bacterial membrane, resulting in intracellular leakage and eventually killing the KPC-KP cells.
Microcystis aeruginosa is a cyanobacterium that produces a variety of cyclic heptapeptide toxins in freshwater. The protective effects of the macromolecular container cucurbit[7]uril (CB7) were evaluated using mouse models of cyanotoxin-induced liver damage. Biochemical analysis of liver function was performed to gauge the extent of liver damage after exposure to cyanobacterial crude extract [CCE; LD50 = 35 mg/kg body weight; intraperitoneal (i.p.)] in the absence or presence of CB7 (35 mg/kg body weight, i.p.). CCE injection resulted in liver enlargement, potentiated the activities of alanine aminotransferase (ALT) and glutathione S-transferase (GST), increased lipid peroxidation (LPO), and reduced protein phosphatase 1 (PP1) activity. CCE-induced liver enlargement, ALT and GST activities, and LPO were significantly reduced when CB7 was coadministered. Moreover, the CCE-induced decline of PP1 activity was also ameliorated in the presence of CB7. Treatment with CB7 alone did not affect liver function, which exhibited a dose tolerance of 100 mg/kg body wt. Overall, our results illustrated that the addition of CB7 significantly reduced CCE-induced hepatotoxicity (P < 0.05).
Safoof-e-Pathar phori (SPP) is an Unani poly-herbomineral formulation, which has for a long time been used as a medicine due to its antiurolithiatic activity, as per the Unani Pharmacopoeia. This powder formulation is prepared using six different plant/mineral constituents. In this study, we explored the antiurolithiatic and antioxidant potentials of SPP (at 700 and 1,000 mg/kg) in albino Wistar rats with urolithiasis induced by 0.75% ethylene glycol (EG) and 1% ammonium chloride (AC). Long-term oral toxicity studies were performed according to the Organization for Economic Co-operation and Development (OECD) guidelines for 90 days at an oral dose of 700 mg/kg of SPP. The EG urolithiatic toxicant group had significantly higher levels of urinary calcium, serum creatinine, blood urea, and tissue lipid peroxidation and significantly (p < 0.001 vs control) lower levels of urinary sodium and potassium than the normal control group. Histopathological examination revealed the presence of refractile crystals in the tubular epithelial cell and damage to proximal tubular epithelium in the toxicant group but not in the SPP treatment groups. Treatment of SPP at 700 and 1,000 mg/kg significantly (p < 0.001 vs toxicant) lowered urinary calcium, serum creatinine, blood urea, and lipid peroxidation in urolithiatic rats, 21 days after induction of urolithiasis compared to the toxicant group. A long-term oral toxicity study revealed the normal growth of animals without any significant change in hematological, hepatic, and renal parameters; there was no evidence of abnormal histology of the heart, kidney, liver, spleen, or stomach tissues. These results suggest the usefulness of SPP as an antiurolithiatic and an antioxidant agent, and long-term daily oral consumption of SPP was found to be safe in albino Wistar rats for up to 3 months. Thus, SPP may be safe for clinical use as an antiurolithiatic formulation.
The study was couducted to investigate the effects of gamma irradiation and CO₂ on flavonoid content and leaf gas exchange in C.asiatica. For flavonoid determination, the design was a split split plot based on Randomized Complete Block Design (RCBD). For other parameters, the designs were split plots. Statistical tests revealed significant differences in flavonoid contents of Centella asiatica leaves between different growth stages and various CO₂ treatments. CO₂ 400, G20 (400 = ambient CO₂; G20 = Plants exposed to 20 Gy) showed 82.90% higher total flavonoid content (TFC) in the 5th week than CO₂ 400 as control at its best harvest time (4th week). Increasing the concentration of CO₂ from 400 to 800 μmol/mol had significant effects on TFC and harvesting time. In fact, 800 μmol/mol resulted in 171.1% and 66.62% increases in TFC for control and irradiated plants, respectively. Moreover, increasing CO₂ concentration reduced the harvesting time to three and four weeks for control and irradiated plants, respectively. Enhancing CO₂ to 800 µmol/mol resulted in a 193.30% (CO₂ 800) increase in leaf biomass compared to 400 µmol/mol and 226.34% enhancement in irradiated plants (CO₂ 800, G20) [800 = Ambient CO₂; G20 = Plants exposed to 20 Gy] than CO₂ 400, G20. In addition, the CO₂ 800, G20 had the highest amount of flavonoid*biomass in the 4th week. The results of this study indicated that all elevated CO₂ treatments had higher PN than the ambient ones. The findings showed that when CO₂ level increased from 400 to 800 µmol/mol, stomatal conductance, leaf intercellular CO₂ and transpiration rate had the tendency to decrease. However, water use efficiency increased in response to elevated CO₂ concentration. Returning to the findings of this study, it is now possible to state that the proposed method (combined CO₂ and gamma irradiation) has the potential to increase the product value by reducing the time to harvest, increasing the yield per unit area via boosting photosynthesis capacity, as well as increasing biochemicals (flavonoids) per gram DM.