α-Mangostin, one of the major constituents of Garcinia mangostana, has been reported to possess several biological activities, including antioxidant, anti-inflammatory, antibacterial, and cytotoxic activities associated with the inhibition of cell proliferation and activation of apoptosis. However, the cellular signaling pathway mediated by α-mangostin has not been firmly established. To investigate the cellular activities of α-mangostin, human cancer cells, MCF-7 and MCF-7-CR cells, were treated with α-mangostin to measure the cellular responses, including cytotoxicity, protein-protein interaction, and protein expression. Cancer cells stably expressed Myc-BCL-XL and HA-MOAP-1 were also included in the studies to delineate the cell signaling events mediated by α-mangostin. Our results showed that the apoptosis signaling mediated by α-mangostin involves the upregulation of endogenous MOAP-1, which interacts with α-mangostin activated BAX (act-BAX) while downregulating the expression of BCL-XL. Moreover, α-mangostin was found to induce BAX oligomerization, the release of mitochondrial cytochrome C, and activation of caspase in MCF-7 cells. In overexpression studies, MCF-7 cells and spheroids stably expressed HA-MOAP-1 and Myc-BCL-XL exhibited differential chemosensitivity toward α-mangostin in which the stable clones expressing HA-MOAP-1 and MYC-BCL-XL were chemosensitive and chemoresistant to the apoptosis signaling events mediated by α-mangostin, respectively, when compared to untreated cells. Together, the data suggest that the cytotoxicity of α-mangostin involves the activation of MOAP-1 tumor suppressor and its interaction with act-BAX, leading to mitochondria dysfunction and cell death.
Physalis minima L. is reputed for having anticancer property. In this study, the chloroform extract of this plant exhibited remarkable cytotoxic activities on NCI-H23 (human lung adenocarcinoma) cell line at dose- and time-dependent manners (after 24, 48 and 72 h of incubation). Analysis of cell-death mechanism demonstrated that the extract exerted apoptotic programed cell death in NCI-H23 cells with typical DNA fragmentation, which is a biochemical hallmark of apoptosis. Morphological observation using transmission electron microscope (TEM) also displayed apoptotic characteristics in the treated cells, including clumping and margination of chromatins, followed by convolution of the nuclear and budding of the cells to produce membrane-bound apoptotic bodies. Different stages of apoptotic programed cell death as well as phosphatidylserine externalization were confirmed using annexin V and propidium iodide staining. Furthermore, acute exposure to the extract produced a significant regulation of c-myc, caspase-3 and p53 mRNA expression in this cell line. Due to its apoptotic effect on NCI-H23 cells, it is strongly suggested that the extract could be further developed as an anticancer drug.
Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS). In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA). KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.
The protective effect of tualang honey (TH) on neuroinflammation and caspase-3 activity in rat cerebral cortex, cerebellum, and brainstem after kainic acid- (KA-) induced status epilepticus was investigated. Male Sprague-Dawley rats were pretreated orally with TH (1.0 g/kg body weight) five times at 12 h intervals. KA (15 mg/kg body weight) was injected subcutaneously 30 min after last oral treatment. Rats were sacrificed at 2 h, 24 h, and 48 h after KA administration. Neuroinflammation markers and caspase-3 activity were analyzed in different brain regions 2 h, 24 h, and 48 h after KA administration. Administration of KA induced epileptic seizures. KA caused significant (p < 0.05) increase in the level of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), glial fibrillary acidic protein (GFAP), allograft inflammatory factor 1 (AIF-1), and cyclooxygenase-2 (COX-2) and increase in the caspase-3 activity in the rat cerebral cortex, cerebellum, and brainstem at multiple time points. Pretreatment with TH significantly (p < 0.05) reduced the elevation of TNF-α, IL-1β, GFAP, AIF-1, and COX-2 level in those brain regions at multiple time points and attenuated the increased caspase-3 activity in the cerebral cortex. In conclusion, TH reduced neuroinflammation and caspase-3 activity after kainic acid- (KA-) induced status epilepticus.
The current study was designed to evaluate the in vitro cytotoxicity effect of a phenylbutenoid dimer, cis-3-(3',4'-dimethoxyphenyl)-4-[(E)-3 (‴) ,4 (‴) -dimethoxystyryl]cyclohex-1-ene (ZC-B11) isolated from the rhizome of Zingiber cassumunar on various cancer cell line, and normal human blood mononuclear cells, and to further investigate the involvement of apoptosis-related proteins that leads, to the probable pathway in which apoptosis is triggered. Cytotoxicity test using MTT assay showed selective inhibition of ZC-B11 towards T-acute lymphoblastic leukemia cells, CEMss, with an IC50 value of 7.11 ± 0.240 μ g/mL, which did not reveal cytotoxic effects towards normal human blood mononuclear cells (IC50 > 50 μ g/mL). Morphology assessments demonstrated distinctive morphological changes corresponding to a typical apoptosis. ZC-B11 also arrested cell cycle progression at S phase and causes DNA fragmentation in CEMss cells. Decline of mitochondrial membrane potential was also determined qualitatively. In the apoptosis-related protein determination, ZC-B11 was found to significantly upregulate Bax, caspase 3/7, caspase 9, cytochrome c, and SMAC and downregulate Bcl-2, HSP70, and XIAP, but did not affect caspase 8, p53, and BID. These results demonstrated for the first time the apoptogenic property of ZC-B11 on CEMss cell line, leading to the programmed cell death via intrinsic mitochondrial pathway of apoptosis induction.
Persicaria hydropiper (L.) Delarbre, belonging to Polygonaceae family, is a common weed found in most of the temperate countries including Bangladesh, China, Malaysia, and Japan. The plant is also referred to as "marsh pepper" or "smart weed." It appears to be a useful herb with evidence-based medicinal properties. The present work addresses the botanical description, traditional uses, phytochemistry, pharmacology, and toxicology of P. hydropiper. All plant parts have been commonly used in the traditional systems of medicines. Flavonoids are the major group of phytochemical components followed by drimane-type sesquiterpenes and sesquiterpenoids, as well as phenylpropanoids. Different extracts and plant parts showed remarkable pharmacological activities including antioxidant, antibacterial, antifungal, antihelminth, antifeedant, cytotoxicity, anti-inflammatory, antinociceptive, oestrogenicity, antifertility, antiadipogenicity, and neuroprotection. Mutagenicity and acute and subchronic toxicities of the plant were also reported. P. hydropiper has tremendous medicinal properties that could further be investigated for the development of evidence-based herbal products.
This study investigated the effects of α-tocopherol and palm oil tocotrienol supplementations on bone fracture healing in postmenopausal osteoporosis rats. 32 female Sprague-Dawley rats were divided into four groups. The first group was sham operated (SO), while the others were ovariectomised. After 2 months, the right femora were fractured under anesthesia and fixed with K-wire. The SO and ovariectomised-control rats (OVXC) were given olive oil (vehicle), while both the alpha-tocopherol (ATF) and tocotrienol-enriched fraction (TEF) groups were given alpha-tocopherol and tocotrienol-enriched fraction, respectively, at the dose of 60 mg/kg via oral gavages 6 days per week for 8 weeks. The rats were then euthanized and the femora dissected out for bone biomechanical testing to assess their strength. The callous of the TEF group had significantly higher stress parameter than the SO and OVXC groups. Only the SO group showed significantly higher strain parameter compared to the other treatment groups. The load parameter of the OVXC and ATF groups was significantly lower than the SO group. There was no significant difference in the Young's modulus between the groups. In conclusion, tocotrienol is better than α-tocopherol in improving the biomechanical properties of the fracture callous in postmenopausal osteoporosis rat model.
Osteoporosis is considered a serious debilitating disease. Cosmos caudatus (ulam raja), a plant containing antioxidant compounds and minerals, may be used to treat and prevent osteoporosis. This study determines the effectiveness of C. caudatus as bone protective agent in postmenopausal osteoporosis rat model. Thirty-two female rats, aged 3 months old, were divided into 4 groups. Group one was sham operated (sham) while group two was ovariectomized. These two groups were given ionized water by forced feeding. Groups three and four were ovariectomized and given calcium 1% ad libitum and force-fed with C. caudatus at the dose of 500 mg/kg, respectively. Treatments were given six days per week for a period of eight weeks. Body weight was monitored every week and structural bone histomorphometry analyses of the femur bones were performed. Ovariectomy decreased trabecular bone volume (BV/TV), decreased trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). Both calcium 1% and 500 mg/kg C. caudatus reversed the above structural bone histomorphometric parameters to normal level. C. caudatus shows better effect compared to calcium 1% on trabecular number (Tb.N) and trabecular separation (Tb.Sp). Therefore, Cosmos caudatus 500 mg/kg has the potential to act as the therapeutic agent to restore bone damage in postmenopausal women.
Nigella sativa seeds (NS) has been used traditionally for various illnesses. The most abundant and active component of NS is thymoquinone (TQ). Animal studies have shown that NS and TQ may be used for the treatment of diabetes-induced osteoporosis and for the promotion of fracture healing. The mechanism involved is unclear, but it was postulated that the antioxidative, and anti-inflammatory activities may play some roles in the treatment of osteoporosis as this bone disease has been linked to oxidative stress and inflammation. This paper highlights studies on the antiosteoporotic effects of NS and TQ, the mechanisms behind these effects and their safety profiles. NS and TQ were shown to inhibit inflammatory cytokines such as interleukin-1 and 6 and the transcription factor, nuclear factor κB. NS and TQ were found to be safe at the current dosage for supplementation in human with precautions in children and pregnant women. Both NS and TQ have shown potential as antiosteoporotic agent but more animal and clinical studies are required to further assess their antiosteoporotic efficacies.
Statins are HMGCoA reductase inhibitors and had been demonstrated to stimulate bone formation in rodents after high oral doses. Observational studies on patients treated with oral statins were varied. Delta-tocotrienol had been found to stimulate the cleavage of HMGCoA reductase and inhibit its activity. Tocotrienols were found to have both catabolic and anabolic effects on bone in different animal models of osteoporosis. The current study aimed to ascertain the effects of delta-tocotrienol and lovastatin combination on biochemical and static bone histomorphometric parameters in a postmenopausal rat model at clinically tolerable doses. 48 Sprague Dawley female rats were randomly divided into 6 groups: (1) baseline control group; (2) sham-operated control group; (3) ovariectomised control group; (4) ovariectomised and 11 mg/kg lovastatin; (5) ovariectomised and 60 mg/kg delta-tocotrienol; (6) ovariectomised and 60 mg/kg delta-tocotrienol + 11 mg/kg lovastatin. These treatments were given daily via oral gavage for 8 weeks. Delta-tocotrienol plus lovastatin treatment significantly increased bone formation and reduced bone resorption compared to the other groups. Therefore, the combined treatment may have synergistic or additive effects and have the potential to be used as an antiosteoporotic agent in patients who are at risk of both osteoporosis and hypercholesterolemia, especially in postmenopausal women.
Virgin coconut oil (VCO) was found to have antioxidant property due to its high polyphenol content. The aim of this study was to investigate the effect of the virgin coconut oil on lipid peroxidation in the bone of an osteoporotic rat model. Normal female Sprague-Dawley rats aged 3 months old were randomly divided into 4 groups, with 8 rats in each group: baseline, sham, ovariectomised (OVX) control group, and OVX given 8% VCO in the diet for six weeks. The oxidative status of the bone was assessed by measuring the index of lipid peroxidation, which is malondialdehyde (MDA) concentration, as well as the endogenous antioxidant enzymes glutathione peroxidase (GPX) and superoxide dismutase (SOD) in the tibia at the end of the study. The results showed that there was a significant decrease in MDA levels in the OVX-VCO group compared to control group. Ovariectomised rats treated with VCO also had significantly higher GPX concentration. The SOD level seemed to be increased in the OVX-VCO group compared to OVX-control group. In conclusion, VCO prevented lipid peroxidation and increased the antioxidant enzymes in the osteoporotic rat model.
Postmenopausal osteoporotic bone loss occurs mainly due to cessation of ovarian function, a condition associated with increased free radicals. Vitamin E, a lipid-soluble vitamin, is a potent antioxidant which can scavenge free radicals in the body. In this study, we investigated the effects of alpha-tocopherol and pure tocotrienol on bone microarchitecture and cellular parameters in ovariectomized rats. Three-month-old female Wistar rats were randomly divided into ovariectomized control, sham-operated, and ovariectomized rats treated with either alpha-tocopherol or tocotrienol. Their femurs were taken at the end of the four-week study period for bone histomorphometric analysis. Ovariectomy causes bone loss in the control group as shown by reduction in both trabecular volume (BV/TV) and trabecular number (Tb.N) and an increase in trabecular separation (Tb.S). The increase in osteoclast surface (Oc.S) and osteoblast surface (Ob.S) in ovariectomy indicates an increase in bone turnover rate. Treatment with either alpha-tocopherol or tocotrienol prevents the reduction in BV/TV and Tb.N as well as the increase in Tb.S, while reducing the Oc.S and increasing the Ob.S. In conclusion, the two forms of vitamin E were able to prevent bone loss due to ovariectomy. Both tocotrienol and alpha-tocopherol exert similar effects in preserving bone microarchitecture in estrogen-deficient rat model.
Oxidative stress and free radicals have been implicated in the pathogenesis of osteoporosis. Therefore, antioxidant compounds have the potential to be used in the prevention and treatment of the disease. In this study, we investigated the effects of virgin coconut oil (VCO) on bone microarchitecture in a postmenopausal osteoporosis rat model. VCO is a different form of coconut oil as it is rich with antioxidants. Three-month-old female rats were randomly grouped into baseline, sham-operated, ovariectomized control (Ovx), and ovariectomized rats fed with 8% VCO in their diet for six weeks (Ovx+VCO). Bone histomorphometry of the right femora was carried out at the end of the study. Rats supplemented with VCO had a significantly greater bone volume and trabecular number while trabecular separation was lower than the Ovx group. In conclusion, VCO was effective in maintaining bone structure and preventing bone loss in estrogen-deficient rat model.
Lymphatic filariasis is a parasitic infection that causes a devastating public health and socioeconomic burden with an estimated infection of over 120 million individuals worldwide. The infection is caused by three closely related nematode parasites, namely, Wuchereria bancrofti, Brugia malayi, and B. timori, which are transmitted to human through mosquitoes of Anopheles, Culex, and Aedes genera. The species have many ecological variants and are diversified in terms of their genetic fingerprint. The rapid spread of the disease and the genetic diversification cause the lymphatic filarial parasites to respond differently to diagnostic and therapeutic interventions. This in turn prompts the current challenge encountered in its management. Furthermore, most of the chemical medications used are characterized by adverse side effects. These complications urgently warrant intense prospecting on bio-chemicals that have potent efficacy against either the filarial worms or thier vector. In lieu of this, we presented a review on recent literature that reported the efficacy of filaricidal biochemicals and those employed as vector control agents. In addition, methods used for biochemical extraction, screening procedures, and structure of the bioactive compounds were also presented.
In recent years, natural products, which originate from plants, animals, and fungi, together with their bioactive compounds have been intensively explored and studied for their therapeutic potentials for various diseases such as cardiovascular, diabetes, hypertension, reproductive, cancer, and neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis are characterized by the progressive dysfunction and loss of neuronal structure and function that resulted in the neuronal cell death. Since the multifactorial pathological mechanisms are associated with neurodegeneration, targeting multiple mechanisms of actions and neuroprotection approach, which involves preventing cell death and restoring the function to damaged neurons, could be promising strategies for the prevention and therapeutic of neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for the treatment of neurodegenerative diseases. This review focused on the therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.
A wide range of medicinal and aromatic plants (MAPs) have been explored for their essential oils in the past few decades. Essential oils are complex volatile compounds, synthesized naturally in different plant parts during the process of secondary metabolism. Essential oils have great potential in the field of biomedicine as they effectively destroy several bacterial, fungal, and viral pathogens. The presence of different types of aldehydes, phenolics, terpenes, and other antimicrobial compounds means that the essential oils are effective against a diverse range of pathogens. The reactivity of essential oil depends upon the nature, composition, and orientation of its functional groups. The aim of this article is to review the antimicrobial potential of essential oils secreted from MAPs and their possible mechanisms of action against human pathogens. This comprehensive review will benefit researchers who wish to explore the potential of essential oils in the development of novel broad-spectrum key molecules against a broad range of drug-resistant pathogenic microbes.
This study evaluates the phytochemistry, antioxidant, and antimicrobial effects of Plectranthus amboinicus leaves extracted in different solvents. The methanol extract contained the highest total phenolic (94.37 ± 1.24 mg GAE/g) and flavonoid contents (26.90 ± 1.35 mg RE/g) and exhibited the highest DPPH scavenging activity (90.13 ± 3.32%) followed by the acetone extract (80.23 ± 3.26%) at 500 μg/mL concentration. Similarly, the highest ferric ion reduction potential (849.63 ± 30.95 μM of Fe (II)/g dry weight) was exhibited by the methanol extract followed by the acetone extract (695.92 ± 25.44 μM of Fe (II)/g dry weight). The methanol extract showed greater antimicrobial activity against all the tested pathogens (Bacillus subtilis, Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans). However, both hexane and acetone extracts failed to inhibit E. coli. S. aureus and C. albicans were more susceptible to all the extracts. Further, GC-MS analysis confirmed the occurrence of a total 46 phytocompounds in different solvent extracts. Some of the major compounds included carvacrol (37.7%), tetracontane (16.6%), squalene (15.6%), tetrapentacontane (13.7%), and Phytol (12.9%). In conclusion, extraction solvents influenced the recovery of phytocompounds and the highest pharmacological activities of the methanol extract could be correlated to the presence of additional bioactive compounds.
Since primitive times, herbs have been extensively used in conventional remedies for boosting cognitive impairment and age-associated memory loss. It is mentioned that medicinal plants have a variety of dynamic components, and they have become a prominent choice for synthetic medications for the care of cognitive and associated disorders. Herbal remedies have played a major role in the progression of medicine, and many advanced drugs have already been developed. Many studies have endorsed practicing herbal remedies with phytoconstituents, for healing Alzheimer's disease (AD). All the information in this article was collated from selected research papers from online scientific databases, such as PubMed, Web of Science, and Scopus. The aim of this article is to convey the potential of herbal remedies for the prospect management of Alzheimer's and related diseases. Herbal remedies may be useful in the discovery and advancement of drugs, thus extending new leads for neurodegenerative diseases such as AD. Nanocarriers play a significant role in delivering herbal medicaments to a specific target. Therefore, many drugs have been described for the management of age-linked complaints such as dementia, AD, and the like. Several phytochemicals are capable of managing AD, but their therapeutic claims are restricted due to their lower solubility and metabolism. These limitations of natural therapeutics can be overcome by using a targeted nanocarrier system. This article will provide the primitive remedies as well as the development of herbal remedies for AD management.
Hypercholesterolemia is the major risk factor that leads to atherosclerosis. Nowadays, alternative treatment using medicinal plants gained much attention since the usage of statins leads to adverse health effects, especially liver and muscle toxicity. This study was designed to investigate the hypocholesterolemic and antiatherosclerotic effects of Basella alba (B. alba) using hypercholesterolemia-induced rabbits. Twenty New Zealand white rabbits were divided into 5 groups and fed with varying diets: normal diet, 2% high cholesterol diet (HCD), 2% HCD + 10 mg/kg simvastatin, 2% HCD + 100 mg/kg B. alba extract, and 2% HCD + 200 mg/kg B. alba extract, respectively. The treatment with B. alba extract significantly lowered the levels of total cholesterol, LDL, and triglycerides and increased HDL and antioxidant enzymes (SOD and GPx) levels. The elevated levels of liver enzymes (AST and ALT) and creatine kinase were noted in hypercholesterolemic and statin treated groups indicating liver and muscle injuries. Treatment with B. alba extract also significantly suppressed the aortic plaque formation and reduced the intima: media ratio as observed in simvastatin-treated group. This is the first in vivo study on B. alba that suggests its potential as an alternative therapeutic agent for hypercholesterolemia and atherosclerosis.
Osteoporosis in elderly men is now becoming an alarming health issue due to its relation with a higher mortality rate compared to osteoporosis in women. Androgen deficiency (hypogonadism) is one of the major factors of male osteoporosis and it can be treated with testosterone replacement therapy (TRT). However, one medicinal plant, Eurycoma longifolia Jack (EL), can be used as an alternative treatment to prevent and treat male osteoporosis without causing the side effects associated with TRT. EL exerts proandrogenic effects that enhance testosterone level, as well as stimulate osteoblast proliferation and osteoclast apoptosis. This will maintain bone remodelling activity and reduce bone loss. Phytochemical components of EL may also prevent osteoporosis via its antioxidative property. Hence, EL has the potential as a complementary treatment for male osteoporosis.