Oligochaeta ramosa (Roxb.) Extract Regulates Lipid Metabolism and Exerts Hepatoprotective Effects in Cadmium-Induced Hepatic Injury in Rats.

Environmental pollutants present a potential source of toxicity when exposed to humans. The study was aimed at investigating the potential of Oligochaeta ramosa (Roxb.) as a hepatoprotective agent in cadmium-induced hepatotoxicity causing lipid profile disturbance. The aqueous methanolic (30 : 70 v/v) extract of O. ramosa Roxb. (AME.Or) was subjected to preliminary phytochemical analysis, whereas the antioxidant activity of its constituents was investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The hepatoprotective and antihyperlipidemic effects of AME.Or was investigated by dividing animals into five groups (A-E). Animals were either treated with normal saline or CdCl2 (6.5 mg/kg, intraperitoneally) followed by treatment with silymarin (100 mg/kg), or AME.Or (200 mg/kg) and AME.Or (400 mg/kg) for consecutive three weeks. Blood samples were collected, and the serum lipid profile was assessed on the 11th and 21st day of treatment. Histopathological analysis was performed after euthanization. In vitro analysis of AME.Or revealed 64% inhibition as free radicals scavenging potential during DPPH, total phenolic content (TPC) (79.92 mgGAE/g), and total flavonoids content (TFC) (38.75 mgRE/g). The group intoxicated with CdCl2 showed significantly high (p ≤ 0.05) levels of the liver function indicators and lipid profile than in the control group. The higher dose of AME.Or (400 mg/kg) significantly decreased the aspartate aminotransferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), total bilirubin (p ≤ 0.001), decreased total cholesterol and triglycerides (p ≤ 0.01) while significantly increased high density lipoprotein (HDL; p ≤ 0.01) as compared to the intoxicated group. The histopathological analysis of the liver revealed signs of necrosis in the intoxicated group, while AME.Or treated groups showed marked improvement. The findings accentuate the therapeutic importance of O. ramosa (Roxb.) as a hepatoprotective remedy.

Anti-inflammatory effect of simvastatin by impeding TNF-α and interleukin-1ß pathways: antiangiogenic activity of simvastatin and simvastatin-loaded silver nanoparticles.

PURPOSE: The present study was carried out to evaluate anti-inflammatory and antiangiogenic attributes of simvastatin and its nanofilms containing silver nanoparticles. METHODS: Silver nanoparticles and simvastatin-loaded nanocomposite (SNSN) films were formulated by using polymeric solution (pectin + sericin) through casting solution method. Different in vitro and in vivo anti-inflammatory assays were performed. In addition, chick chorioallantoic membrane assay (CAM) was also employed for angiogenesis activity. RESULTS: FTIR spectra of the film depicted the presence of intact simvastatin. Differential scanning calorimetry exhibited no endothermic expression in F9 film thermogram. The simvastatin release from all films exhibited a burst effect. Cotton-pellet induced granuloma model study showed that high dose of simvastatin and indomethacin produced comparable (p < 0.05) anti-inflammatory effect. Noteworthy, RT-PCR showed dose-dependent, anti-oedematous effect of simvastatin through downregulation of serum TNF-α and interleukin-1ß levels. While results of CAM assay exhibited remarkable anti-angiogenic potential of SNSN films showing dissolved blood vessels network macroscopically. CONCLUSION: To reiterate, simvastatin and its SNSN films can add significant contribution to the field of biomedicines due to their promising anti-inflammatory and antiangiogenic properties, however, clinical studies are required to validate their commercial use.

TGF-ß1 signaling can worsen NAFLD with liver fibrosis backdrop.

Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by the accumulation of fats in the liver. Relatively benign NAFLD often progresses to fibrosis, cirrhosis, and liver malignancies. Although NAFLD precedes fibrosis, continuous lipid overload keeps fueling fibrosis and the process of disease progression remains unhindered. It is well known that TGF-ß1 plays its part in liver fibrosis, yet its effects on liver lipid overload remain unknown. As TGF-ß1 signaling has been increasingly attempted to manage liver fibrosis, its actions on the primary suspect (NAFLD) are easily ignored. The complex interaction of inflammatory stress and lipid accumulation aided by mediators scuh as pro-inflammatory interleukins and TGF-ß1 forms the basis of NAFLD progression. Anticipatorily, the inhibition of TGF-ß1 signaling during anti-fibrotic treatment should reverse the NAFLD though the data remain scattered on this subject to date. TGF-ß1 signaling pathway is an important drug target in liver fibrosis and abundant literature is available on it, but its direct effects on NAFLD are rarely studied. This review aims to cover the pathogenesis of NAFLD focusing on the role of the TGF-ß1 in the disease progression, especially in the backdrop of liver fibrosis.

Emerging Trends of Multidrug-Resistant (MDR) and Extensively Drug-Resistant (XDR) Salmonella Typhi in a Tertiary Care Hospital of Lahore, Pakistan.

Salmonella Typhi is a Gram-negative pathogen that causes typhoid fever in humans. The use of antibiotics to treat typhoid has considerably mitigated its fatality risk, but rising multidrug-resistant (MDR) and extensively drug-resistant (XDR) resistance in Pakistan threatens effective treatment. This study determined the prevalence of MDR and XDR S. Typhi at a local hospital in Lahore. Blood samples (n = 3000) were obtained and processed for bacterial identification. Antibiotic susceptibility test was performed using VITEK® 2 Compound 30 System. Statistical data analysis was performed using a Mann-Whitney U and Kruskal-Wallis H test, respectively. The results revealed 600 positive cultures, of which the majority were found to be XDR S. Typhi (46.1%) and MDR S. Typhi (24.5%) strains. The disease burden of resistant Salmonella strains was greater in males (60.67%) than females (39.33%), with the most affected age group being 0-10 years old (70.4 %). In both the outpatient department (OPD) and general ward, the prevalence of XDR S. Typhi cases was found to be alarmingly high (48.24%), followed by MDR S. Typhi (25.04 %). The results of the statistical analysis demonstrated that the incidence of resistance in MDR and XDR S. Typhi strains was not affected by the age as well as the gender of patients (p > 0.05). The occurrence of resistant strains against four tested antibiotics (azithromycin, ciprofloxacin, imipenem, and meropenem) was found to be similar in different wards and among hospitalized and OPD patients (p > 0.05). Maximum resistance was observed against chloramphenicol and ampicillin in the OPD and pediatric ward. Piperacillin/Tazobactam was observed to be the most effective antibiotic, followed by co-amoxiclav (p < 0.001). This study is effective in validating the existence of MDR and XDR S. Typhi in Lahore, where stringent methods should be applied for controlling its spread.

The Adipokine Component in the Molecular Regulation of Cancer Cell Survival, Proliferation and Metastasis.

A hormonal imbalance may disrupt the rigorously monitored cellular microenvironment by hampering the natural homeostatic mechanisms. The most common example of such hormonal glitch could be seen in obesity where the uprise in adipokine levels is in virtue of the expanding bulk of adipose tissue. Such aberrant endocrine signaling disrupts the regulation of cellular fate, rendering the cells to live in a tumor supportive microenvironment. Previously, it was believed that the adipokines support cancer proliferation and metastasis with no direct involvement in neoplastic transformations and tumorigenesis. However, the recent studies have reported discrete mechanisms that establish the direct involvement of adipokine signaling in tumorigenesis. Moreover, the individual adipokine profile of the patients has never been considered in the prognosis and staging of the disease. Hence, the present manuscript has focused on the reported extensive mechanisms that culminate the basis of poor prognosis and diminished survival rate in obese cancer patients.

Anticancer, antimicrobial and antioxidant potential of sterically tuned bis-N-heterocyclic salts.

The current study was conducted to evaluate the antimicrobial, antioxidant, antileishmanial and cytotoxic potential of designed derivatives of 1,1'-(1,3-phenylenebis(methylene))bis(3-alkyl/aryl-1H-benzimidazol-3-ium) salts. The antibacterial potential of the test compounds was investigated against Staphylococcus aureus, Pseudomonas aeruginosa and two methicillin-resistant S. aureus (MRSA) strains (MRSA10, MRSA11), where compound 6 showed the best results. For brine shrimp lethality bioassay (BSLB), compound 6 again showed up to 100% mortality at 200 µg/mL and 56.7% mortality at 6.25 µg/mL. Antileishmanial assay was performed against Leishmania tropica at 20 µg/mL dosage, where 6 showed the most promising activity with 16.26% survival (83.74% mortality; IC50=14.63 µg/mL). The anticancer potential of the selected benzimidazole derivatives was evaluated against two selected cell lines (human colorectal cancer, HCT-116 and breast adenocarcinoma, MCF-7) using sulforhodamine B (SRB) assay. Compound 6 was found to be the most effective cytotoxic compound with 75% inhibition of HCT-116 proliferation at 1 mg/mL concentration. Succinctly, 6 exhibited impressive pharmacological potential that might be attributed to its higher lipophilic character owing to the longer N-substituted alkyl chains when compared to the other test compounds.

Evaluation of in vitro and in vivo anti-inflammatory effects of (-)-pseudosemiglabrin, a major phytoconstituent isolated from Tephrosia apollinea (Delile) DC.

ETHNOPHARMACOLOGICAL RELEVANCE: Tephrosia apollinea (Delile) DC (Leguminosae) has been used in folk medicine in Arabian countries to treat inflammatory disorders. The plant has been described to treat swelling, bone fracture, bronchitis, cough, earache and wounds. AIM OF THE STUDY: the current study aims to evaluate the anti-inflammatory properties of the major active phytoconstituent of T. apollinea and elucidate the mechanisms by which it inhibits inflammation in vitro and in vivo. MATERIAL AND METHODS: The compound, (-)-pseudosemiglabrin (SSG) was isolated as a major component from the aerial parts of T. apollinea using column chromatography techniques. Sub-chronic in vivo anti-inflammatory effect of SSG was assessed using cotton pellet granuloma assay in SD rats and serum levels of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and nitric oxide (NO) were measured, whereas, tail flick assay was performed to assess the analgesic effect of SSG. Furthermore, the anti-inflammatory effects of SSG were confirmed by measuring the levels of IL-1, TNF-α, and NO in vitro using human macrophage cell lines (U937). In addition COX inhibition assay was also conducted in cells-free system. In silico study was performed to dock SSG in cyclooxygenase enzymes and opioid receptor to predict its structure-activity and molecular mechanism. RESULTS: SSG displayed potential inhibition of granuloma tissue in rats and significantly (P<0.05) lowered the production of cytokines (TNF- α and IL-1) in vivo as well as human macrophages. Further investigation revealed that, SSG selectively inhibited COX-2 by 60% with negligible effect on COX-1. The selectivity of SSG towards COX-2 was confirmed in silico wherein, SSG demonstrated significant binding affinity with binding energy (-9.42kcal/mol). The binding found to be through covalent energy with Ser-530 amino acid residue of the active pocket of COX-2. SSG was found to prolong the flick tail time in mice by two folds. Further computational studies reveal that SSG binds to opioid receptor (µ-OR) through Ile-144 and Thr-218 with affinity two folds compared to the reference compounds, codeine and aspirin. CONCLUSION: In the present study the major phytoconstituent (-)-pseudosemiglabrin (SSG) from the aerial parts of T. apollinea demonstrated potent anti-inflammatory effect by inhibiting of granuloma tissue in rats and prolonging the tail flick time in mice. Investigation of levels of pro-inflammatory cytokines in SSG-treated rats and human macrophages demonstrated that SSG significantly inhibited TNF-α and IL-1. Also SSG showed selective inhibitory effect towards COX-2. In silico study exhibited pronounced binding affinity between SSG and µ-opioid receptor better than that of codeine and aspirin. The obtained results justify the use of aerial parts of T. apollinea to treat various inflammatory diseases and indicate that (-)-pseudosemiglabrin has a great potential to be further developed as a promising anti-inflammatory drug.

Macrophage and colon tumor cells as targets for a binuclear silver(I) N-heterocyclic carbene complex, an anti-inflammatory and apoptosis mediator.

Chronic inflammation intensifies the risk for malignant neoplasm, indicating that curbing inflammation could be a valid strategy to prevent or cure cancer. Cancer and inflammation are inter-related diseases and many anti-inflammatory agents are also used in chemotherapy. Earlier, we have reported a series of novel ligands and respective binuclear Ag(I)-NHC complexes (NHC=N-heterocyclic carbene) with potential anticancer activity. In the present study, a newly synthesized salt (II) and respective Ag(I)-NHC complex (III) of comparable molecular framework were prepared for a further detailed study. Preliminarily, II and III were screened against HCT-116 and PC-3 cells, wherein III showed better results than II. Both the compounds showed negligible toxicity against normal CCD-18Co cells. In FAM-FLICA caspase assay, III remarkably induced caspase-3/7 in HCT-116 cells most probably by tumor necrosis factor-alpha (TNF-α) independent intrinsic pathway and significantly inhibited in vitro synthesis of cytokines, interleukin-1 (IL-1) and TNF-α in human macrophages (U937 cells). In a cell-free system, both the compounds inhibited cyclooxygenase (COX) activities, with III being more selective towards COX-2. The results revealed that III has strong antiproliferative property selectively against colorectal tumor cells which could be attributed to its pro-apoptotic and anti-inflammatory abilities.

Vernonia amygdalina simultaneously suppresses gluconeogenesis and potentiates glucose oxidation via the pentose phosphate pathway in streptozotocin-induced diabetic rats.

BACKGROUND: This study evaluated the impact of Vernonia amygdalina (VA) on the transcription of key enzymes involved in cellular modulation of glucose in streptozotocin-induced diabetic rats in a bid to understand the possible anti-diabetic mechanism of VA. METHODS: The chloroform fraction of VA (200 mg/kg and 400 mg/kg body weight) was administered to SDRs for 7 and 14 days. Thereafter, the expression (transcription) of key carbohydrate regulatory genes was evaluated in selected tissues - adipose, muscle and liver. Also, the body weight and blood glucose changes were monitored. RESULTS: A 14-day administration of 200 mg and 400 mg of the extract and metformin (500 mg/kg) showed a striking decrease (P <0.05) in the expression of the gluconeogenic enzymes - fructose 1,6-bisphosphatase, phosphoenol pyruvate carboxykinase and glucose 6-phosphatase in the liver and muscle compared to the diabetic control. These genes were highly expressed in tissues of untreated diabetic rats (P <0.05) indicating severe gluconeogenesis. Furthermore, the extract as well as metformin significantly increased glucose oxidation via the pentose phosphate pathway (PPP) i.e. increased expression of the glucose 6-phosphate dehydrogenase (G6PDH) gene (P <0.05) in the liver. Conversely, the expression of the G6PDH in the muscle and adipose tissues significantly decreased (P <0.05), suggesting enhanced utilization of NADPH and ribose in the clearance of reactive oxygen species and for expression of other relevant genes respectively. Also, transcription of the cell proliferation regulatory enzyme, phosphatidylinositol 3-kinase increased in the liver, but decreased in the muscle and adipose tissues (P <0.05) upon treatment with the extract or metformin, implying that the liver responded to the VA and metformin treatments more than other organs. The extract administration also caused a decrease in the expression of key enzymes of glycolysis namely hexokinase and phosphofructokinase, suggestive of a glucose sparing for ribose and NADPH production in PPP. CONCLUSION: Overall, data obtained in this study suggest that VA exerts little or no effect on glycolysis; rather, it may achieve its anti-diabetic action by a simultaneous suppression of gluconeogenesis and potentiation of glucose oxidation via PPP pathway, almost exclusively in the liver.

Anti-inflammatory and antioxidant activities of the methanol extract of Gynura segetum leaf.

Gynura segetum, family Compositae, is a cultivated species and can be found growing in the tropical regions of Indonesia and Malaysia. The plant is known for its use for the treatment of cancer, inflammation, diabetes, hypertension and skin afflictions. In the current study, in vivo anti-inflammatory effect of the methanol extract G. segetum leaf and its antioxidant effect in vitro have been investigated for the first time. The in vitro antioxidant activities of the methanol extract were measured using common methods including total phenolic content; total flavonoid content; scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ß-carotene bleaching assays. The in vivo anti-inflammatory activities were tested using the cotton pellet implanted animal model. The measurement of pro-inflammatory cytokine (TNF-α and IL-1) levels in the blood samples of the rats was carried out by using ELISA kits. The inhibitory activity on cyclooxygenase (COX) enzyme of methanol extract was also evaluated. The methanol extract exhibited good antioxidant activity which is associated with their total phenolic and flavonoid contents. Methanol extract strongly inhibited the granuloma tissue formation in rats and the anti-inflammatory potential was mediated through the inhibition of pro-inflammatory cytokines and COX-2 enzyme activities. Taken together, the present study suggests that G. segetum's leaf is a natural source of antioxidants and has potential therapeutic benefits against chronic inflammation.

Increased aqueous solubility and proapoptotic activity of potassium koetjapate against human colorectal cancer cells.

OBJECTIVES: Recently, we have isolated koetjapic acid (KA) from Sandoricum koetjape and identified its selective anticancer potentiality against colorectal carcinoma. KA is quite likely to be useful as a systemic anticancer agent against colorectal malignancy. However, with extremely low solubility, KA has to be converted into a biocompatible solubilized form without compromising the bioefficacy. Objective of this study is to enhance solubility of KA and to evaluate anticancer efficacy of potassium koetjapate in human colorectal cancer cells. METHODS: (2-Hydroxypropyl)-ß-cyclodextrin inclusion complex and solid dispersions (carboxymethyl cellulose, polyvinylpyrrolidone and sodium lauryl sulphate) of KA were prepared. In addition, a salt of KA, potassium koetjapate was synthesized. KEY FINDINGS: Potassium koetjapate demonstrated higher solubility than the other tested formulations with enhanced cytotoxicity against HCT 116 cells. The enhanced efficacy of potassium koetjapate is attributed to apoptotic induction of nuclear condensation and disruption of mitochondrial membrane potential in the cells. Interestingly, potassium koetjapate was found to be safe in rats after oral administration (LD50 > 2000 mg/kg). CONCLUSIONS: The salt formulation of KA appears to modulate the capability of the parent compound by enhancing its solubility and improves its bioefficacy against colon cancer cells, suggesting attractive roles for its applications in medicine.

Multi-constituent synergism is responsible for anti-inflammatory effect of Azadirachta indica leaf extract.

CONTEXT: Azadirachta indica A. Juss. (Meliaceaes) leaves have been used traditionally to treat swelling and rheumatism in Indian cultures. OBJECTIVE: To fractionate A. indica leaf extracts using bioactivity guided manner for identification of the active anti-inflammatory principles. MATERIALS AND METHODS: Polarity-gradient sequential extracts (petroleum ether, chloroform, methanol, and water) of A. indica leaves were screened for their anti-inflammatory potential using the carrageenan-induced rat paw edema model (1 g/kg). The chloroform extract was sequentially fractionated to obtain n-hexane (F-1), n-hexane-chloroform (F-2), and chloroform (F-3) fractions and their inhibitory effect on rat paw edema was evaluated (500 mg/kg). Inhibitory effect of F-2 on granuloma formation, plasma interleukin (IL-1), and tumor necrosis factor (TNF-α) was assessed at the doses of 100, 200, and 400 mg/kg using the cotton pellet assay in rats. Three sub-fractions (SF-1, SF-2, and SF-3) were obtained upon chromatography of F-2, and their inhibitory effect on cyclooxygenase was assessed at 200 µg/mL concentration. The sub-fractions were subjected to gas chromatography-mass spectrometry (GC-MS). RESULTS: All the extracts showed significant anti-inflammatory effect; however, chloroform extract was the most effective against paw edema (53.25% inhibition). The three fractions of chloroform extract showed significant effect, while F-2 being the most potent (51.02%). F-2 demonstrated dose-dependent inhibition of granuloma and cytokines. Interestingly, all the sub-fractions of F-2 inhibited COX-1 and COX-2 with almost equal potential. GC-MS revealed that chemically the sub-fractions were totally different from each other. DISCUSSION AND CONCLUSION: Anti-inflammatory effect of A. indica is a result of cumulative and synergistic effects of diversified constituents with varying polarities that collectively exert the effect via suppression of cyclo-oxygenases and cytokines (IL-1 and TNF-α).

Ethyl-p-methoxycinnamate isolated from Kaempferia galanga inhibits inflammation by suppressing interleukin-1, tumor necrosis factor-α, and angiogenesis by blocking endothelial functions.

OBJECTIVE: The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga. METHODS: The anti-inflammatory effects of ethyl-p-methoxycinnamate were assessed using the cotton pellet granuloma assay in rats, whereby the levels of interleukin-1 and tumor necrosis factor-α were measured in the animals' blood. In addition, the levels of interleukin, tumor necrosis factor, and nitric oxide were measured in vitro using the human macrophage cell line (U937). The analgesic effects of ethyl-p-methoxycinnamate were assessed by the tail flick assay in rats. The anti-angiogenic effects were evaluated first by the rat aortic ring assay and, subsequently, by assessing the inhibitory effects of ethyl-p-methoxycinnamate on vascular endothelial growth factor, proliferation, migration, and tube formation in human umbilical vein endothelial cells. RESULTS: Ethyl-p-methoxycinnamate strongly inhibited granuloma tissue formation in rats. It prolonged the tail flick time in rats by more than two-fold compared with the control animals. The inhibition of interleukin and tumor necrosis factor by ethyl-p-methoxycinnamate was significant in both in vivo and in vitro models; however, only a moderate inhibition of nitric oxide was observed in macrophages. Furthermore, ethyl-p-methoxycinnamate considerably inhibited microvessel sprouting from the rat aorta. These mechanistic studies showed that ethyl-p-methoxycinnamate strongly inhibited the differentiation and migration of endothelial cells, which was further confirmed by the reduced level of vascular endothelial growth factor. CONCLUSION: Ethyl-p-methoxycinnamate exhibits significant anti-inflammatory potential by inhibiting pro-inflammatory cytokines and angiogenesis, thus inhibiting the main functions of endothelial cells. Thus, ethyl-p-methoxycinnamate could be a promising therapeutic agent for the treatment of inflammatory and angiogenesis-related diseases.

Ethyl-p-methoxycinnamate isolated from kaempferia galanga inhibits inflammation by suppressing interleukin-1, tumor necrosis factor-α, and angiogenesis by blocking endothelial functions

OBJECTIVE: The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga. METHODS: The anti-inflammatory effects of ethyl-p-methoxycinnamate were assessed using the cotton pellet granuloma assay in rats, whereby the levels of interleukin-1 and tumor necrosis factor-α were measured in the animals' blood. In addition, the levels of interleukin, tumor necrosis factor, and nitric oxide were measured in vitro using the human macrophage cell line (U937). The analgesic effects of ethyl-p-methoxycinnamate were assessed by the tail flick assay in rats. The anti-angiogenic effects were evaluated first by the rat aortic ring assay and, subsequently, by assessing the inhibitory effects of ethyl-p-methoxycinnamate on vascular endothelial growth factor, proliferation, migration, and tube formation in human umbilical vein endothelial cells. RESULTS: Ethyl-p-methoxycinnamate strongly inhibited granuloma tissue formation in rats. It prolonged the tail flick time in rats by more than two-fold compared with the control animals. The inhibition of interleukin and tumor necrosis factor by ethyl-p-methoxycinnamate was significant in both in vivo and in vitro models; however, only a moderate inhibition of nitric oxide was observed in macrophages. Furthermore, ethyl-p-methoxycinnamate considerably inhibited microvessel sprouting from the rat aorta. These mechanistic studies showed that ethyl-p-methoxycinnamate strongly inhibited the differentiation and migration of endothelial cells, which was further confirmed by the reduced level of vascular endothelial growth factor. CONCLUSION: Ethyl-p-methoxycinnamate exhibits significant anti-inflammatory potential by inhibiting pro-inflammatory cytokines and angiogenesis, thus inhibiting the main functions of endothelial cells. Thus, ethyl-p-methoxycinnamate could be a promising therapeutic agent ...

Phytochemistry and medicinal properties of Phaleria macrocarpa (Scheff.) Boerl. extracts.

Phaleria macrocarpa, commonly known as Mahkota dewa is a medicinal plant that is indigenous to Indonesia and Malaysia. Extracts of P. macrocarpa have been used since years in traditional medicine that are evaluated scientifically as well. The extracts are reported for a number of valuable medicinal properties such as anti-cancer, anti-diabetic, anti-hyperlipidemic, anti-inflammatory, anti-bacterial, anti-fungal, anti-oxidant and vasorelaxant effect. The constituents isolated from different parts of P. macrocarpa include Phalerin, gallic acid, Icaricide C, magniferin, mahkoside A, dodecanoic acid, palmitic acid, des-acetylflavicordin-A, flavicordin-A, flavicordin-D, flavicordin-A glucoside, ethyl stearate, lignans, alkaloids andsaponins. The present review is an up-to-date summary of occurrence, botanical description, ethnopharmacology, bioactivity and toxicological studies related to P. macrocarpa.

Bioactivity-guided isolation of ethyl-p-methoxycinnamate, an anti-inflammatory constituent, from Kaempferia galanga L. extracts.

This study evaluated the anti-inflammatory effect of Kaempferia galanga (KG) using an activity-guided approach. KG rhizomes were serially extracted with petroleum ether, chloroform, methanol and water. These extracts (2 g/kg each) were tested for their ability to inhibit carrageenan-induced rat paw edema. The chloroform extract was found to exert the highest inhibition (42.9%) compared to control (p < 0.001), hence it was further fractionated by washing serially with hexane, hexane-chloroform (1:1) and chloroform. The chloroform fraction (1 g/kg) showed the highest inhibitory effect (51.9%, (p < 0.001), on carrageenan-induced edema. This chloroform fraction was further fractionated with hexane-chloroform (1:3) and chloroform, and of the two fractions, the hexane-chloroform sub-fraction was the most effective in inhibiting edema (53.7%, p < 0.001). GC-MS analysis of the active sub-fraction identified ethyl-p-methoxycinnamate (EPMC) as the major component, which was re-crystallized. EPMC dose-dependently inhibited carrageenan-induced edema with an MIC of 100 mg/kg. Moreover, in an in vitro study, EPMC non-selectively inhibited the activities of cyclooxygenases 1 and 2, with IC50 values of 1.12 µM and 0.83 µM respectively. These results validate the anti-inflammatory activity of KG which may be exerted by the inhibition of cyclooxygenases 1 and 2. EPMC isolated from this plant may be the active anti-inflammatory agent.