Evaluation of the female reproductive toxicity of aqueous extract of  Labisia pumila   var. alata  in rats

Ezumi, M F Wan; Amrah, S. S.; Suhaimi, A. W. Mohd; Mohsin, Sahar

doi:10.4103/0253-7613.30760

Cited by 36 publications

(4 citation statements)

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“…LPva has potential as an alternative to ERT for the treatment of postmenopausal osteoporosis. In terms of safety, several toxicity studies have confirmed that LPva is safe [37,38]. While, in terms of its action, LPva has demonstrated phytoestrogenic properties [20,21].…”

Section: Discussionmentioning

confidence: 99%

Labisia pumila regulates bone-related genes expressions in postmenopausal osteoporosis model

Fathilah

Mohamed

Muhammad

et al. 2013

BMC Complement Altern Med

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BackgroundLabisia Pumila var. alata (LPva) has shown potential as an alternative to estrogen replacement therapy (ERT) in prevention of estrogen-deficient osteoporosis. In earlier studies using postmenopausal model, LPva was able to reverse the ovariectomy-induced changes in biochemical markers, bone calcium, bone histomorphometric parameters and biomechanical strength. The mechanism behind these protective effects is unclear but LPva may have regulated factors that regulate bone remodeling. The aim of this study is to determine the bone-protective mechanism of LPva by measuring the expressions of several factors involved in bone formative and resorptive activities namely Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor kappa-B Ligand (RANKL), Macrophage-Colony Stimulating Factor (MCSF) and Bone Morphogenetic Protein-2 (BMP-2).MethodsThirty-two female Wistar rats were randomly divided into four groups: Sham-operated (Sham), ovariectomized control (OVXC), ovariectomized with Labisia pumila var. alata (LPva) and ovariectomized with ERT (Premarin®) (ERT). The LPva and ERT were administered via daily oral gavages at doses of 17.5 mg/kg and 64.5 μg/kg, respectively. Following two months of treatment, the rats were euthanized and the gene expressions of BMP-2, OPG, RANKL and MCSF in the femoral bones were measured using a branch - DNA technique.ResultsThe RANKL gene expression was increased while the OPG and BMP-2 gene expressions were reduced in the OVXC group compared to the SHAM group. There were no significant changes in the MCSF gene expressions among the groups. Treatment with either LPva or ERT was able to prevent these ovariectomy-induced changes in the gene expressions in ovariectomized rats with similar efficacy.ConclusionLPva may protect bone against estrogen deficiency-induced changes by regulating the RANKL, OPG and BMP-2 gene expressions.

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Section: Discussionmentioning

confidence: 99%

Labisia pumila regulates bone-related genes expressions in postmenopausal osteoporosis model

Fathilah

Mohamed

Muhammad

et al. 2013

BMC Complement Altern Med

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“…LP extract has been shown to be safe with LD50 of more than 5.0 g/kg [52]. According to other studies, LP extract was found to exhibit no-adverse-effect-level (NOAEL) at the dose of 50 mg/kg in sub-acute [53], 1000 mg/kg in subchronic [54] and 800 mg/kg in reproductive toxicity studies [52]. In human, the effective doses taken by women are around 500-1000 mg/kg daily.…”

Section: Discussionmentioning

confidence: 99%

The effects of Labisia pumila on postmenopausal osteoporotic rat model: Dose and time-dependent micro-CT analysis

Effendy

Khamis

Soelaiman

et al. 2014

Journal of X-Ray Science and Technology: Clinical Applications

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BACKGROUND: Postmenopausal osteoporosis is best treated and prevented by estrogen replacement therapy (ERT). Although effective, ERT may cause breast cancer, uterine cancer and cardiovascular problems. Labisia pumila var. alata (LP), a herb with phytoestrogenic, antioxidative and anti-inflammatory effects has potential as an ERT alternative. OBJECTIVE: This study aimed to evaluate micro-CT analysis on the effects of LP supplementation on the trabecular microarchitecture of postmenopausal osteoporosis rat model. Micro-CT is an effective tool in detecting changes in trabecular bone structure and providing a three dimensional information which may replace other conventional bone analysis methods. METHODS: Ninety-six female Sprague-Dawley rats (4 to 5 months old) were randomly divided into six groups of baseline group (BL) Sham-operated (Sham), ovariectomised control (OVXC), ovariectomised with 64.5 μg/kg of Premarin (ERT), ovariectomised with 20 mg/kg of LP (LP20) and ovariectomised with 100 mg/kg of LP at (LP100). The vehicle (deionized water), Premarin and LP were given via daily oral gavages for three, six and nine weeks of treatment periods. Rats in BL group were euthanized before the start of the study, while other rats were euthanized after completion of their treatments. Femora were dissected out and trabecular bone microarchitecture analysed with micro-CT. RESULTS: Micro-CT analysis of OVXC rats revealed significant osteoporotic changes in connectivity density, trabecular bone volume, trabecular thickness, trabecular separation and trabecular number. Both ERT and LP were able to reverse all the OVX-induced bone changes with the best results seen with 100 mg/kg of LP for nine weeks duration of treatment. CONCLUSION: Micro-CT provides accurate and reliable information on trabecular bone parameters which aid in the diagnosis and treatment of osteoporosis. LP supplementation at 100 mg/kg was more effective than ERT in reversing ovariectomyinduced bone changes. Further studies are required to explore the potential of LP as ERT alternative in the treatment and prevention of postmenopausal osteoporosis.

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“…Twenty-four rats were divided into 4 groups (n = 6), namely control healthy, non-treated diabetic control (D), D+LP at 150 mg/ kg, and D+LP at 300 mg/kg rats. The LP did not show teratogenic effects on pregnant Sprague-Dawley rats at doses of 2, 20, 200, 400, 1,000 mg kg -1 day -1 (Wan Ezumi et al, 2007). The doses used were based on previous reports (Madzuki et al, 2018;Mohd Fuad et al, 2017) and the experiment was conducted over 13 weeks.…”

Section: Diabetes Induction With Streptozotocin (Stz) and Treatmentsmentioning

confidence: 99%

“…L. pumila indicated good cardiovascular protective properties, safety, and efficacy but has not previously been demonstrated to be anti-diabetic in vivo (Effendy et al, 2014). L. pumila was not teratogenic on pregnant Sprague Dawley rats at doses of 2-1,000 mg kg -1 day -1 (Wan Ezumi et al, 2007). This study investigates whether L. pumila ethanol extract (LP) could mitigate diabetic eye pathogenesis and if it could be correlated to changes in serum TNFα, VEGF, PGE2, claudin-1, and GSH levels, as a possible mode of action.…”

Section: Introductionmentioning

confidence: 99%

Gallic acid and myricetin‐rich Labisia pumila extract mitigated multiple diabetic eye disorders in rats

et al. 2021

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Diabetes affected about a quarter of a billion people globally, and one out of four diabetics has eye or vision problems. This study investigated whether gallic acid and myricetin-rich Labisia pumila extract (LP) consumption would help prevent diabetic eye disorders and some probable biochemistry involved relating to inflammation, vascular leakage, and oxidative tension. Male rats were divided into four groups (n = 6), namely healthy control, diabetic non-treated control, and hyperglycemic rats treated with 150 or 300 mg/kg LP. Intraperitoneal injection of 60 mg/kg streptozotocin was used to induce diabetes. Rats were fed in the morning and evening. Diabetic retinopathy was graded in rats using a dilated retinal digital ophthalmoscopy. Rats were sacrificed at 12 weeks and the retina, optic nerve, cornea, lens, sclera, ciliary bodies, iris, and conjunctiva were examined histologically. The diabetic rats consuming LP for 10 weeks showed dose-dependent, histopathologically-reduced eye abnormalities (keratopathy, cataract, sclera, conjunctiva, ciliary bodies, iris, limbus, corneal edema, epithelial barrier inefficiency, shallow punctate keratitis, lower basal layer cell density, retinopathy, glaucoma, and corneal changes). The LP significantly suppressed inflammation [increased serum tumor necrosis factorα (TNFα), prostaglandin-E2 (PGE2)], vascular leakage [claudin-1], abnormal vascularization [vascular endothelial growth factor (VEGF)], oxidative tension [malondialdehyde/reduced glutathione ratio], and hyperglycemia [fasting blood glucose] of the diabetic rats. The LP consumption was significantly protective against diabetic eye disorders and optic nerve dysfunction which were related to inflammation, vascular leakage, abnormal vascularization, and oxidative tension, which most likely influenced eye hemorrhage and collagen cross-linkage. Practical applicationsThe study shows that gallic acid and myricetin-rich Labisia pumila (LP) leaf consumption may be used as a complementary therapy for managing diabetes (fasting blood glucose) and preventing diabetic eye disorders (keratopathy, cataract, sclera, conjunctiva, ciliary bodies, iris, limbus, corneal edema, epithelial barrier inefficiency, shallow punctate keratitis, lower basal layer cell density, retinopathy, glaucoma, and corneal abnormalities). The LP consumptions reduced the serum biomarkers for inflammation (serum tumor necrosis factorα TNFα; prostaglandin-E2), vascular

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Evaluation of the female reproductive toxicity of aqueous extract of Labisia pumila var. alata in rats

Cited by 36 publications

References 0 publications

Labisia pumila regulates bone-related genes expressions in postmenopausal osteoporosis model

Labisia pumila regulates bone-related genes expressions in postmenopausal osteoporosis model

The effects of Labisia pumila on postmenopausal osteoporotic rat model: Dose and time-dependent micro-CT analysis

Gallic acid and myricetin‐rich Labisia pumila extract mitigated multiple diabetic eye disorders in rats

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