Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor that regulates lipid and glucose metabolism. We investigated the effects of Labisia pumila (LP) standardized water extract on PPARgamma transcriptional activity in adipocytes in vitro and in vivo. We used a rat model of dihydrotestosterone- (DHT-) induced polycystic ovary syndrome (PCOS), a condition characterized by insulin resistance. At 9 weeks of age, the PCOS rats were randomly subdivided into two groups: PCOS-LP (50 mg/kg/day of LP) and PCOS-control (1 mL of deionised water) for 4-5 weeks on the same schedule. Real-time RT-PCR was performed to determine the PPARgamma mRNA levels. LP upregulated PPARgamma mRNA level by 40% in the PCOS rats. Western blot analysis further demonstrated the increased PPARgamma protein levels in parallel with upregulation in mRNA. These observations were further proven by adipocytes culture. Differentiated 3T3-L1 adipocytes were treated with final concentration of 100 μ g/mL LP and compared to untreated control and 10 μ M of rosiglitazone (in type of thiazolidinediones). LP increased PPARgamma expressions at both mRNA and protein levels and enhanced the effect of glucose uptake in the insulin-resistant cells. The data suggest that LP may ameliorate insulin resistance in adipocytes via the upregulation of PPARgamma pathway.
Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of microarchitecture of bone tissue which is attributed to various factors including inflammation. Women are more likely to develop osteoporosis than men due to reduction in estrogen during menopause which leads to decline in bone-formation and increase in bone-resorption activity. Estrogen is able to suppress production of proinflammatory cytokines such as IL-1, IL-6, IL-7, and TNF-α. This is why these cytokines are elevated in postmenopausal women. Studies have shown that estrogen reduction is able to stimulate focal inflammation in bone. Labisia pumila (LP) which is known to exert phytoestrogenic effect can be used as an alternative to ERT which can produce positive effects on bone without causing side effects. LP contains antioxidant as well as exerting anti-inflammatory effect which can act as free radical scavenger, thus inhibiting TNF-α production and COX-2 expression which leads to decline in RANKL expression, resulting in reduction in osteoclast activity which consequently reduces bone loss. Hence, it is the phytoestrogenic, anti-inflammatory, and antioxidative properties that make LP an effective agent against osteoporosis.
There is growing evidence that inflammation may be one of the causal factors of osteoporosis. Several cytokines such as IL-1, IL-6, RANKL, OPG, and M-CSF were implicated in the pathogenesis of osteoporosis. These cytokines are important determinants of osteoclast differentiation and its bone resorptive activity. Anticytokine therapy using cytokine antagonists such as IL-receptor antagonist and TNF-binding protein was able to suppress the activity of the respective cytokines and prevent bone loss. Several animal studies have shown that vitamin E in the forms of palm-derived tocotrienol and α-tocopherol may prevent osteoporosis in rat models by suppressing IL-1 and IL-6. Free radicals are known to activate transcription factor NFκB which leads to the production of bone resorbing cytokines. Vitamin E, a potent antioxidant, may be able to neutralise free radicals before they could activate NFκB, therefore suppressing cytokine production and osteoporosis. Vitamin E has also been shown to inhibit COX-2, the enzyme involved in inflammatory reactions. Of the two types of vitamin E studied, tocotrienol seemed to be better than tocopherol in terms of its ability to suppress bone-resorbing cytokines.
Medicinal plants continue to play an important role in modern medications and healthcare as consumers generally believe that most of them cause fewer or milder adverse effects than the conventional modern medicines. In order to use the plants as a source of medicinal agents, the bioactive compounds are usually extracted from plants. Therefore, the extraction of bioactive compounds from medicinal plants is a crucial step in producing plant-derived drugs. One of the bioactive compounds isolable from medicinal plants, orientin, is often used in various bioactivity studies due to its extensive beneficial properties. The extraction of orientin in different medicinal plants and its medicinal properties, which include antioxidant, antiaging, antiviral, antibacterial, anti-inflammation, vasodilatation and cardioprotective, radiation protective, neuroprotective, antidepressant-like, antiadipogenesis, and antinociceptive effects, are discussed in detail in this review.
The present study was designed to evaluate the acute and chronic antidepressant effect of genistein in combination with amitriptyline in mice. Animals were divided into six groups (n = 6) for treatment with water, genistein, or amitriptyline, either alone or in combination for ten days. Animals were subjected to locomotor activity testing; tail suspension test (TST); and forced swim test (FST) and immobility time was recorded on day one and day ten. Acute treatment of all treatment groups did not significantly reduce the immobility time (p > 0.05). Chronic treatment of combination of genistein (10 mg/kg) and amitriptyline (5 mg/kg and 10 mg/kg) significantly reduced the immobility time as compared to control group (p < 0.001) and was comparable to amitriptyline alone (10 mg/kg). However, no changes in anti-immobility activity in combination of subeffective doses of genistein (5 mg/kg) and amitriptyline (5 mg/kg) were observed. Genistein at its standard dose (10 mg/kg) rendered synergistic effects in combination with subeffective dose of amitriptyline (5 mg/kg) and additive effects in combination with therapeutic dose of amitriptyline (10 mg/kg).
Doxorubicin (DOX) is a potent anticancer agent with cytotoxic effects which limit its clinical usage. This effect is due to its nonselective nature causing injury to the cells as a result of reactive free oxygen radical's release. Cockleshell-derived calcium carbonate nanoparticle (CS-CaCO3NP) is a pH-responsive carrier with targeted delivery potentials. This study aimed at evaluating the toxicity effects of repeated dose administration of DOX-loaded CS-CaCO3NP in healthy dogs. Fifteen dogs with an average body weight of 15 kg were randomized equally into 5 groups. Dogs were subjected to 5 doses at every 3-week interval with (i) normal saline, (ii) DOX, 30 mg/m2, and the experimental groups: CS-CaCO3NP-DOX at (iii) high dose, 50 mg/m2, (iv) clinical dose, 30 mg/m2, and (v) low dose, 20 mg/m2. Radiographs, electrocardiography, and blood samples were collected before every treatment for haematology, serum biochemistry, and cardiac injury assessment. Heart and kidney tissues were harvested after euthanasia for histological and ultrastructural evaluation. The cumulative dose of DOX 150 mg/m2 over 15 weeks revealed significant effects on body weight, blood cells, functional enzymes, and cardiac injury biomarkers with alterations in electrocardiogram, myocardium, and renal tissue morphology. However, the dogs given CS-CaCO3NP-DOX 150 mg/m2 and below did not show any significant change in toxicity biomarker as compared to those given normal saline. The study confirmed the safety of repeated dose administration of CS-CaCO3NP-DOX (30 mg/m2) for 5 cycles in dogs. This finding offers opportunity to dogs with cancer that might require long-term administration of DOX without adverse effects.
This article aims to provide detailed information on Malaysian plants used for treating inflammation. An extensive search on electronic databases including PubMed, Google Scholar, Scopus, and ScienceDirect and conference papers was done to find relevant articles on anti-inflammatory activity of Malaysian medicinal plants. The keyword search terms used were "inflammation," "Malaysia," "medicinal plants," "mechanisms," "in vitro," and "in vivo." As a result, 96 articles on anti-inflammatory activity of Malaysian medicinal plants were found and further reviewed. Forty-six (46) plants (in vitro) and 30 plants (in vivo) have been identified to possess anti-inflammatory activity where two plants, Melicope ptelefolia (Tenggek burung) and Portulaca oleracea (Gelang pasir), were reported to have the strongest anti-inflammatory activity of more than 90% at a concentration of 250 µg/ml. It was showed that the activity was mainly due to the occurrence of diverse naturally occurring phytochemicals from diverse groups such as flavonoids, coumarins, alkaloids, steroids, benzophenone, triterpenoids, curcuminoids, and cinnamic acid. Hence, this current review is a detailed discussion on the potential of Malaysian medicinal plants as an anti-inflammatory agent from the previous studies. However, further investigation on the possible underlying mechanisms and isolation of active compounds still remains to be investigated.
Spondyloarthritis or spondyloarthropathy (SpA) is a group of related rheumatic disorders, which presents with axial and nonaxial features, affecting structures within the musculoskeletal system, as well as other bodily systems. Both pharmacological and nonpharmacological therapeutic options are available for SpA. For decades, nonsteroidal anti-inflammatory drugs (NSAIDs) have been used as the first-line drugs to treat the disease. Research has shown that other than pain relief, NSAIDs have disease-modifying effects in SpA. However, to achieve these effects, continuous and/or long-term NSAID use is usually required. This review will give an overview of SpA, discuss NSAIDs and their disease-modifying effects in SpA, and highlight some of the important adverse effects of long-term and continuous NSAID use, particularly those related to the gastrointestinal, renal, and cardiovascular systems.
The nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed by medical practitioners in many clinical conditions for the symptomatic treatment of pain and fever. Due to their anti-inflammatory properties, these drugs have been investigated for their anticancer effects in numerous studies. This is because chronic inflammation has long been linked to carcinogenesis. As such, anti-inflammatory drugs are believed to play a role in cancer treatment and prevention. In the past few decades, research has shown that NSAIDs may decrease the risk of certain types of cancer. However, there is also a growing body of research that proves the contrary. Furthermore, NSAIDs are well known for many side effects, including some life-threatening ones. This review will discuss the relationship between chronic inflammation and cancer, the role of NSAIDs in cancer prevention and cancer promotion, and some of the potentially lethal side effects of these drugs.
Both honeybees (Apis spp.) and stingless bees (Trigona spp.) produce honeys with high nutritional and therapeutics value. Until recently, the information regarding potential health benefits of stingless bee honey (SBH) in medical databases is still scarce as compared to the common European bee honey (EBH) which is well known for their properties as therapeutic agents. Although there have been very few reports on SBH, empirically these products would have similar therapeutic quality as the EBH. In addition, due to the structure of the nest, few studies reported that the antimicrobial activity of SBH is a little bit stronger than EBH. Therefore, the composition of both the types of honey as well as the traditional uses and clinical applications were compared. The results of various studies on EBH and SBH from tissue culture research to randomised control clinical trials were collated in this review. Interestingly, there are many therapeutic properties that are unique to SBH. Therefore, SBH has a great potential to be developed for modern medicinal uses.
Different solvent extracts of Pereskia bleo leaves were evaluated for total phenolic content (TPC) and antioxidant activities based on the Folin-Ciocalteu test and DPPH scavenging activities. The antibacterial activities against four bacteria, namely, Gram-positive bacteria: Streptococcus pyogenes ATCC 19615 (SP) and Staphylococcus aureus ATCC 29737 (SA) and Gram-negative bacteria: Escherichia coli ATCC 10536 (EC) and Pseudomonas aeruginosa ATCC 9027 (PA), were also performed based on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. The findings demonstrated that both the methanolic and chloroform extracts displayed strong activities against SA, SP, EC, and PA while the hexane extract demonstrated the weakest activities towards all the four bacteria. The methanolic extract also exhibited higher TPC and possessed higher antioxidant activity with the IC50 value 33.83 µg/mL compared to the chloroform and hexane extracts. As such, the methanolic extract has a higher ability to scavenge free radical compared to other extracts. Due to the interesting result, activities are shown by the methanolic and chloroform crude extracts of P. bleo; hence, the study has been extended to the isolation of bioactive compounds to uncover its great potential as a natural source for antibacterial and antioxidant agents.