Zingiber zerumbet, a plant native to tropical and subtropical Asia, has a vast range of traditional uses and has been continuously studied for its medicinal properties. However, a systematic methodological approach in evidence synthesis on the plant's efficacy is lacking, and there is a need to elicit the current research status of this plant. This scoping review was conducted to systematically explore and collate the available scientific evidence on the efficacy of Z. zerumbet and its main phytoconstituents in various formulations, their biological mechanisms, and their safety. Results included 54 articles consisting of animal studies, while there were no published human studies. Only half of the included studies provided adequate reporting on the quality-related details of Z. zerumbet formulations. Identified pharmacological activities were analgesic, anti-inflammatory, anti-diabetic, anti-hyperlipidemic, anti-neoplastic, immunomodulatory, antioxidant, antipyretic, hepatoprotective, nephroprotective, gastroprotective, and locomotor-reducing activities. Notably, the ethanolic extract of Z. zerumbet was found to be well tolerated for up to 28 days. In conclusion, Z. zerumbet and zerumbone have various pharmacological effects, especially in analgesic and anti-inflammatory models. However, there is still a pressing need for comprehensive safety data to conduct clinical trials.
Osteoporosis is a systemic and metabolic bone disease that usually occurs in postmenopausal women, which mainly manifests as bone loss and increased bone fragility that both facilitate fracture. However, few drugs for osteoporosis have shown good efficacy and limited side effects. Vaccarin has demonstrated its antiosteoporosis effects by inhibiting the formation and osteolytic activities of osteoclasts in our previous investigation. In this study, multivariate statistical analysis and ultrahigh-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry were used to analyze the serum metabolites of ovariectomized mice treated with or without vaccarin. As a result, 9 serum metabolites were identified as biomarkers. The metabolic levels of 3 crucial biomarkers, namely, lysophosphatidylcholine [22 : 6, (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)], 1-linoleoylglycerophosphocholine and 1-palmitoyl-Sn-glycero-3-phosphocholine, that were correlated with glycerophospholipid metabolism increased and then decreased significantly after vaccarin treatment. Molecular docking analysis and osteoclasts differentiation experiment further revealed that vaccarin may bind with phospholipase A2 and downregulated its activity to reduce the osteoclastogenesis. Therefore, the occurrence of osteoporosis is closely related with glycerophospholipid metabolism disorders, and vaccarin exerts antiosteoporosis effects by reducing the levels of glycerophospholipid metabolites.
Glycation, the non-enzymatic binding of glucose to free amino groups of an amino acid, yields irreversible heterogeneous compounds known as advanced glycation end products. Those products play a significant role in diabetic complications. In the present article we briefly discuss the contribution of advanced glycation end products to the pathogenesis of diabetic complications, such as atherosclerosis, diabetic retinopathy, nephropathy, neuropathy, and wound healing. Then we mention the various mechanisms by which polyphenols inhibit the formation of advanced glycation end products. Finally, recent supporting documents are presented to clarify the inhibitory effects of polyphenols on the formation of advanced glycation end products. Phytochemicals apply several antiglycation mechanisms, including glucose metabolism, amelioration of oxidative stress, scavenging of dicarbonyl species, and up/down-regulation of gene expression. To utilize polyphenols in order to remedy diabetic complications, we must explore, examine and clarify the action mechanisms of the components of polyphenols.
The present study aimed to investigate standardized ethanol extracts of fruit and leaves of Piper sarmentosum for their in vivo antioxidant activity in rats using a CCl (4)-induced oxidative stress model. The standardization was based on the quantification of the markers pellitorine, sarmentine and sarmentosine by high performance liquid chromatography (HPLC), and determination of total primary and secondary metabolites. The rats, divided into 7 groups each (n = 6), were used as follows: group 1 (CCl (4), negative control), group 2 (untreated, control), groups 3 and 4 (fruit extract 250 and 500 mg/kg, respectively), groups 5 and 6 (leaf extract 250 and 500 mg/kg, respectively) and group 7 (vitamin-E 100 mg/kg, positive control). The doses were administered orally for 14 days; 4 h following the last dose, a single dose of CCl (4) (1.5 mg/kg) was given orally to all the groups except group 2, and after 24 h, blood and liver of each animal were obtained. Analysis of plasma and liver homogenate exhibited significant preservation of markers of antioxidant activity, total plasma antioxidant activity (TPAA), total protein (TP), superoxide dismutase (SOD), catalase (CAT), and thiobarbituric acid reactive species (TBARS), in the pretreated groups as compared to the CCl (4) group (p < 0.05). Histology of the liver also evidenced the protection of hepatocytes against CCl (4) metabolites in the pretreated groups. The results of this study indicate the IN VIVO antioxidant activity of both extracts of the plant, which may be valuable to combat diseases involving free radicals.
Among the quassinoids isolated from Eurycoma longifolia Jack, eurycomanone was identified as the most potent and toxic inhibitor of the chloroquine-resistant Gombak A isolate of Plasmodium falciparum. Several diacylated derivatives of eurycomanone, 1,15-di-O-isovaleryleurycomanone, 1,15-di-O-(3,3-dimethylacryloyl)- eurycomanone and 1,15-di-O-benzoyleurycomanone were synthesized by direct acylation with the respective acid chlorides. The monoacylated 15-O-isovaleryleurycomanone was synthesized by selective protection of the other hydroxy groups of eurycomanone with trimethylsilyl trifluoromethanesulphonate to enable the exclusive acylation of its C-15 hydroxy group. This was followed by the removal of the protecting groups with citric acid. The diacylated eurycomanones exhibited lower antiplasmodial activity against the Gombak A isolates and lower toxicity in the brine shrimp assay when compared to eurycomanone. In contrast, the monoacylated derivative displayed comparable antiplasmodial potency to eurycomanone, but its toxicity was reduced. Thus, preliminary studies of the synthesized acylated eurycomanones have shown that acylation only at the C-15 hydroxy group may be worthy of further antimalarial investigation.
Common Gram-positive clinical pathogens are showing an increasing trend for resistance to conventional antimicrobial agents. New drugs with potent antibacterial activities are urgently needed to remediate this problem. Halogenated compounds isolated from several species of the red algae genus Laurencia were examined for their antibacterial activity against 22 strains of human pathogenic bacteria, 7 strains of which were antibiotic-resistant bacteria. Four phenolic sesquiterpenes and a polybrominated indole showed wide spectra of antibacterial activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus faecalis and E. faecium (VRE). In addition, laurinterol and allolaurinterol displayed potent bactericidal activity against three strains of MRSA at 3.13 microg mL(-1), and three strains of vancomycin-susceptible Enterococcus, at 3.13 microg mL(-1) and 6.25 microg mL(-1), respectively.
The growing demand and commercial value of black pepper (Piper nigrum) has resulted in considerable interest in developing suitable and cost-effective methods for chemical characterization and quality evaluation purposes. In the current study, an extensive set of oil samples (n = 23) that were extracted by steam distillation from black pepper seeds was investigated to compare the chemical profiles of samples originating from nine major producing countries, as well as to identify potential chemical markers for quality evaluation. The twenty-two most abundant volatile compounds, mainly terpenes, in these oils were determined by conventional GC/MS analysis. Principal component analysis with this set of data revealed distinct clusters for samples that originated from China and Malaysia. Relatively low concentrations of sabinene (
The methanolic extract of the leaves of CASSIA ALATA was sequentially partitioned in increasing polarity to afford the hexane, chloroform, butanol and residual extract. Crude extracts were evaluated against MRSA using the agar well diffusion assay. The butanol and chloroform extracts both exhibited inhibition against MRSA with inhibition indexes of 1.03 +/- 0.16 and 0.78 +/- 0.07 at the concentration of 50 mg/mL. The butanol extracts were further purified using silica gel and reverse phase chromatography to afford kaempferol ( 1), kaempferol 3- O-beta-glucopyranoside ( 2), kaempferol 3- O-gentiobioside ( 3) and aloe emodin ( 4). The four constituents showed varying degrees of inhibition against MRSA. Both 1 and 4 exhibited MIC (50) values of 13.0 +/- 1.5 microg/mL and 12.0 +/- 1.5 microg/mL, respectively. The kaempferol glycosides 2 and 3 were less active with MIC (50) values of 83.0 +/- 0.9 microg/mL and 560.0 +/- 1.2 microg/mL, respectively. A free hydroxyl group at C-3 of the flavonol structure is a structural requirement for the inhibition of MRSA.
A phytochemical study has been carried out on CH2Cl2 extract of Alphonsea cylindrica leaves, resulting in the isolation of three new morphinan alkaloids. They are kinomenine (1: ), N-methylkinomenine (2: ), and hydroxymethylkinomenine (3: ). The structures of these compounds were elucidated by extensive spectroscopic analysis (1D and 2D NMR, IR, UV, HRESIMS) and comparison with the data reported in literature for similar alkaloids. Kinomenine (1: ) and N-methylkinomenine (2: ) showed weak inhibition against S. aureus (MIC values of 1: and 2: = 500 µg/mL; pIC50 values in 95% C. I. of: 1: = 2.9 to 3.0; 2: = 2.9 to 3.1), while kinomenine (1: ) also showed weak inhibition against E. coli (MIC values of 1: = 500 µg/mL; pIC50 value in 95% C. I. of: 1: = 2.9) by broth microdilution method. The results obtained can be used as future referencefor the discovery of morphinans and the potential of A. cylindrica as an antibacterial source.
Diabetes mellitus (DM) is a metabolic endocrine disorder caused by decreased insulin concentration or poor insulin response. Muntingia calabura (MC) has been used traditionally to reduce blood glucose levels. This study aims to support the traditional claim of MC as a functional food and blood-glucose-lowering regimen. The antidiabetic potential of MC is tested on a streptozotocin-nicotinamide (STZ-NA)-induced diabetic rat model by using the 1H-NMR-based metabolomic approach. Serum biochemical analyses reveal that treatment with 250 mg/kg body weight (bw) standardized freeze-dried (FD) 50% ethanolic MC extract (MCE 250) shows favorable serum creatinine (37.77 ± 3.53 µM), urea (5.98 ± 0.84 mM) and glucose (7.36 ± 0.57 mM) lowering capacity, which was comparable to the standard drug, metformin. The clear separation between diabetic control (DC) and normal group in principal component analysis indicates the successful induction of diabetes in the STZ-NA-induced type 2 diabetic rat model. A total of nine biomarkers, including allantoin, glucose, methylnicotinamide, lactate, hippurate, creatine, dimethylamine, citrate and pyruvate are identified in rats' urinary profile, discriminating DC and normal groups through orthogonal partial least squares-discriminant analysis. Induction of diabetes by STZ-NA is due to alteration in the tricarboxylic acid (TCA) cycle, gluconeogenesis pathway, pyruvate metabolism and nicotinate and nicotinamide metabolism. Oral treatment with MCE 250 in STZ-NA-induced diabetic rats shows improvement in the altered carbohydrate metabolism, cofactor and vitamin metabolic pathway, as well as purine and homocysteine metabolism.
The endophytic fungus Guignardia mangiferae isolated from Ilex cornuta leaves was shown to produce a family of meroterpenes with toll-like receptor 3 regulating activity (1-9), of which 1-3 possessed new structures. The absolute stereochemistry of 1-3 was assigned through a combination of nuclear magnetic resonance experiments, chemical derivation, CD spectra, and single-crystal X-ray diffraction analyses (CuK α ). The precursor labeled cultivation suggests that these meroterpenes are most likely assembled through terpenoid-shikimate pathways. Moreover, meroterpenes 1-3, 5-7, and 9 selectively upregulate, but 4 and 8 downregulate the toll-like receptor 3 expression in mouse dendritic cells at 10.0 µM.
Magnoflorine, a major bioactive metabolite isolated from Tinospora crispa, has been reported for its diverse biochemical and pharmacological properties. However, there is little report on its underlying mechanisms of action on immune responses, particularly on macrophage activation. In this study, we aimed to investigate the effects of magnoflorine, isolated from T. crispa on the pro-inflammatory mediators generation induced by LPS and the concomitant NF-κB, MAPKs, and PI3K-Akt signaling pathways in U937 macrophages. Differentiated U937 macrophages were treated with magnoflorine and the release of pro-inflammatory mediators was evaluated through ELISA, while the relative mRNA expression of the respective mediators was quantified through qRT-PCR. Correspondingly, western blotting was executed to observe the modulatory effects of magnoflorine on the expression of various markers related to NF-κB, MAPK and PI3K-Akt signaling activation in LPS-primed U937 macrophages. Magnoflorine significantly enhanced the upregulation of TNF-α, IL-1β, and PGE2 production as well as COX-2 protein expression. Successively, magnoflorine prompted the mRNA transcription level of these pro-inflammatory mediators. Magnoflorine enhanced the NF-κB activation by prompting p65, IκBα, and IKKα/β phosphorylation as well as IκBα degradation. Besides, magnoflorine treatments concentration-dependently augmented the phosphorylation of JNK, ERK, and p38 MAPKs as well as Akt. The immunoaugmenting effects were further confirmed by investigating the effects of magnoflorine on specific inhibitors, where the treatment with specific inhibitors of NF-κB, MAPKs, and PI3K-Akt proficiently blocked the magnoflorine-triggered TNF-α release and COX-2 expression. Magnoflorine furthermore enhanced the MyD88 and TLR4 upregulation. The results suggest that magnoflorine has high potential on augmenting immune responses.
Zingiber montanum rhizomes are traditionally used for the treatment of numerous human ailments. The present study was carried out to investigate the inhibitory activity of the crude extract, chromatographic fractions, and purified compounds from Z. montanum rhizomes on the migration of MDA-MB-231 cells. The effect of the extract on cell migration was investigated by a scratch assay, which showed significant inhibition in a concentration-dependent manner. Vacuum liquid chromatography on silica gel afforded four fractions (Frs. 1 - 4), which were tested on cell migration in the scratch assay. Frs. 1 and 2 showed the most significant inhibition of MDA-MB-231 cell migration. The effect of the most potent fraction (Fr. 2) was further confirmed in a transwell migration assay. The study of Frs. 1 and 2 by gelatin zymography showed significant inhibition of MMP-9 enzyme activity. Chromatographic separation of Frs. 1 and 2 afforded buddledone A (1: ), zerumbone (2: ), (2E,9E)-6-methoxy-2,9-humuradien-8-one (3: ), zerumbone epoxide (4: ), stigmasterol (5: ), and daucosterol (6: ). In a cell viability assay, compounds 1: - 4: inhibited the viability of MDA-MB-231 cells in a concentration-dependent manner. The study of buddledone A (1: ) and zerumbone epoxide (4: ) on cell migration revealed that 4: significantly inhibited the migration of MDA-MB-231 cells in both scratch and transwell migration assays. The results of the present study may lead to further molecular studies behind the inhibitory activity of zerumbone epoxide (4: ) on cell migration and support the traditional use of Z. montanum rhizomes for the treatment of cancer.