Amala Soumyanath

Oregon Health and Science University, Portland, Oregon, United States

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Publications (10)26.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: We previously showed that a water extract of the medicinal plant Centella asiatica (CAW) attenuates amyloid-β (Aβ)-induced cognitive deficits in vivo, and prevents Aβ-induced cytotoxicity in vitro. Yet the neuroprotective mechanism of CAW is unknown. Objective: The goal of this study was to identify biochemical pathways altered by CAW using in vitro models of Aβ toxicity. Methods: The effects of CAW on aberrations in antioxidant response, calcium homeostasis, and mitochondrial function induced by Aβ were evaluated in MC65 and SH-SY5Y neuroblastoma cells. Results: CAW decreased intracellular reactive oxygen species and calcium levels elevated in response to Aβ, and induced the expression of antioxidant response genes in both cell lines. In SH-SY5Y cells, CAW increased basal and maximal oxygen consumption without altering spare capacity, and attenuated Aβ-induced decreases in mitochondrial respiration. CAW also prevented Aβ-induced decreases in ATP and induced the expression of mitochondrial genes and proteins in both cell types. Caffeoylquinic acids from CAW were shown to have a similar effect on antioxidant and mitochondrial gene expression in neuroblastoma cells. Primary rat hippocampal neurons treated with CAW also showed an increase in mitochondrial and antioxidant gene expression. Conclusions: These data suggest an effect of CAW on mitochondrial biogenesis, which in conjunction with activation of antioxidant response genes and normalizing calcium homeostasis, likely contributes to its neuroprotective action against Aβ toxicity.
    Journal of Alzheimer's disease: JAD 01/2015; DOI:10.3233/JAD-142217 · 4.15 Impact Factor
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    ABSTRACT: The accumulation of amyloid-β (Aβ) is a hallmark of Alzheimer's disease and is known to result in neurotoxicity both in vivo and in vitro. We previously demonstrated that treatment with the water extract of Centella asiatica (CAW) improves learning and memory deficits in Tg2576 mice, an animal model of Aβ accumulation. However the active compounds in CAW remain unknown. Here we used two in vitro models of Aβ toxicity to confirm this neuroprotective effect and identify several active constituents of the CAW extract. CAW reduced Aβ-induced cell death and attenuated Aβ-induced changes in tau expression and phosphorylation in both the MC65 and SH-SY5Y neuroblastoma cell lines. We confirmed and quantified the presence of several mono- and dicaffeoylquinic acids (CQAs) in CAW using chromatographic separation coupled to mass spectrometry and ultraviolet spectroscopy. Multiple dicaffeoylquinic acids showed efficacy in protecting MC65 cells against Aβ-induced cytotoxicity. Isochlorogenic acid A and 1,5-dicaffeoylquinic acid were found to be the most abundant CQAs in CAW, and the most active in protecting MC65 cells from Aβ-induced cell death. Both compounds showed neuroprotective activity in MC65 and SH-SY5Y cells at concentrations comparable to their levels in CAW. Each compound not only mitigated Aβ-induced cell death, but was able to attenuate Aβ-induced alterations in tau expression and phosphorylation in both cell lines, as seen with CAW. These data suggest that CQAs are active neuroprotective components in CAW, and therefore are important markers for future studies on CAW standardization, bioavailability, and dosing.
    Journal of Alzheimer's disease: JAD 01/2014; 40(2). DOI:10.3233/JAD-131913 · 4.15 Impact Factor
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    ABSTRACT: Centella asiatica (CA), commonly named gotu kola, is an Ayurvedic herb used to enhance memory and nerve function. To investigate the potential use of CA in Alzheimer's disease (AD), we examined the effects of a water extract of CA (GKW) in the Tg2576 mouse, a murine model of AD with high β-amyloid burden. Orally administered GKW attenuated β-amyloid-associated behavioral abnormalities in these mice. In vitro, GKW protected SH-SY5Y cells and MC65 human neuroblastoma cells from toxicity induced by exogenously added and endogenously generated β-amyloid, respectively. GKW prevented intracellular β-amyloid aggregate formation in MC65 cells. GKW did not show anticholinesterase activity or protect neurons from oxidative damage and glutamate toxicity, mechanisms of current AD therapies. GKW is rich in phenolic compounds and does not contain asiatic acid, a known CA neuroprotective triterpene. CA thus offers a unique therapeutic mechanism and novel active compounds of potential relevance to the treatment of AD.
    02/2012; 2012:381974. DOI:10.1155/2012/381974
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    ABSTRACT: Vitiligo is a depigmentary disease characterized by melanocyte loss attributed most commonly to autoimmune mechanisms. Currently vitiligo has a high incidence (1% worldwide) but a poor set of treatment options. Piperine, a compound found in black pepper, is a potential treatment for the depigmentary skin disease vitiligo, due to its ability to stimulate mouse epidermal melanocyte proliferation in vitro and in vivo. The present study investigates the use of multispectral imaging and an image processing technique based on local contrast to quantify the stimulatory effects of piperine on human melanocyte proliferation in reconstructed epidermis. We demonstrate the ability of the imaging method to quantify increased pigmentation in response to piperine treatment. The quantization of melanocyte stimulation by the proposed imaging technique illustrates the potential use of this technology to quickly assess therapeutic responses of vitiligo tissue culture models to treatment non-invasively.
    Proceedings of SPIE - The International Society for Optical Engineering 02/2011; DOI:10.1117/12.875620 · 0.20 Impact Factor
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    ABSTRACT: Piperine and its analogues have been reported to stimulate melanocyte replication in vitro and may be useful in treating the depigmenting disease, vitiligo. To investigate the ability of piperine (PIP) and three analogues to stimulate pigmentation in a strain of sparsely pigmented mice. The test compounds were PIP [5-(3,4-methylenedioxyphenyl)-2,4-pentadienoylpiperidine], tetrahydropiperine [THP, 5-(3,4-methylenedioxyphenyl)-pentanoylpiperidine], a cyclohexyl analogue of piperine [CHP, 5-(3,4-methylenedioxyphenyl)-2,4-pentadienoylcyclohexylamine], and reduced CHP [rCHP, 5-(3,4-methylenedioxyphenyl)-2,4-pentanoylcyclohexylamine]. Sparsely pigmented, HRA/Skh-II mice were randomized to receive topical treatment with test compounds or vehicle twice a day for five days a week, with or without ultraviolet (UV) irradiation on 3 days a week. Treatment was either continuous or interrupted to evaluate fading and repigmentation. Skin inflammation and pigmentation were evaluated regularly during treatment. DOPA+ melanocytes were determined histologically at the termination of treatment. Four weeks of treatment with one of the compounds PIP, THP or rCHP, but not CHP, induced greater pigmentation than vehicle with low levels of inflammation. Additional exposure to UVR led to darker pigmentation than did the compound or UVR alone, and greater numbers of DOPA+ melanocytes were found. The combination produced an even pigmentation pattern, contrasting with the speckled, perifollicular pattern produced by UVR alone. Treatment interruption led to a decrease in pigmentation but not its loss. Repigmentation was achieved by administering one of the compounds, UVR or both, and occurred faster than in naïve mice. Treatment with PIP, THP or rCHP and UVR induced a marked pigmentation response in HRA/Skh-II mice, with clinically better results than UVR alone. This result supports the potential use of these compounds in treating vitiligo.
    British Journal of Dermatology 06/2008; 158(5):941-50. DOI:10.1111/j.1365-2133.2008.08464.x · 4.10 Impact Factor
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    ABSTRACT: Background Piperine and its analogues have been reported to stimulate melanocyte replication in vitro and may be useful in treating the depigmenting disease, vitiligo.Objective To investigate the ability of piperine (PIP) and three analogues to stimulate pigmentation in a strain of sparsely pigmented mice.Methods The test compounds were PIP [5-(3,4-methylenedioxyphenyl)-2,4-pentadienoylpiperidine], tetrahydropiperine [THP, 5-(3,4-methylenedioxyphenyl)-pentanoylpiperidine], a cyclohexyl analogue of piperine [CHP, 5-(3,4-methylenedioxyphenyl)-2,4-pentadienoylcyclohexylamine], and reduced CHP [rCHP, 5-(3,4-methylenedioxyphenyl)-2,4-pentanoylcyclohexylamine]. Sparsely pigmented, HRA/Skh-II mice were randomized to receive topical treatment with test compounds or vehicle twice a day for five days a week, with or without ultraviolet (UV) irradiation on 3 days a week. Treatment was either continuous or interrupted to evaluate fading and repigmentation. Skin inflammation and pigmentation were evaluated regularly during treatment. DOPA+ melanocytes were determined histologically at the termination of treatment.Results Four weeks of treatment with one of the compounds PIP, THP or rCHP, but not CHP, induced greater pigmentation than vehicle with low levels of inflammation. Additional exposure to UVR led to darker pigmentation than did the compound or UVR alone, and greater numbers of DOPA+ melanocytes were found. The combination produced an even pigmentation pattern, contrasting with the speckled, perifollicular pattern produced by UVR alone. Treatment interruption led to a decrease in pigmentation but not its loss. Repigmentation was achieved by administering one of the compounds, UVR or both, and occurred faster than in naïve mice.Conclusions Treatment with PIP, THP or rCHP and UVR induced a marked pigmentation response in HRA/Skh-II mice, with clinically better results than UVR alone. This result supports the potential use of these compounds in treating vitiligo.
    British Journal of Dermatology 04/2008; 158(5):941 - 950. · 4.10 Impact Factor
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    ABSTRACT: Melanocyte proliferation stimulants are of interest as potential treatments for the depigmentary skin disorder, vitiligo. Piper nigrum L. (Piperaceae) fruit (black pepper) water extract and its main alkaloid, piperine (1), promote melanocyte proliferation in-vitro. A crude chloroform extract of P. nigrum containing piperine was more stimulatory than an equivalent concentration of the pure compound, suggesting the presence of other active components. Piperine (1), guineensine (2), pipericide (3), N-feruloyltyramine (4) and N-isobutyl-2E, 4E-dodecadienamide (5) were isolated from the chloroform extract. Their activity was compared with piperine and with commercial piperlongumine (6) and safrole (7), and synthetically prepared piperettine (8), piperlonguminine (9) and 1-(3, 4-methylenedioxyphenyl)-decane (10). Compounds 6-10 either occur in P. nigrum or are structurally related. Compounds 1, 2, 3, 8 and 9 stimulated melanocyte proliferation, whereas 4, 5, 6, 7 and 10 did not. Comparison of structures suggests that the methylenedioxyphenyl function is essential for melanocyte stimulatory activity. Only those compounds also possessing an amide group were active, although the amino component of the amide group and chain linking it to the methylenedioxyphenyl group can vary. P. nigrum, therefore, contains several amides with the ability to stimulate melanocyte proliferation. This finding supports the traditional use of P. nigrum extracts in vitiligo and provides new lead compounds for drug development for this disease.
    Journal of Pharmacy and Pharmacology 05/2007; 59(4):529-36. DOI:10.1211/jpp.59.4.0007 · 2.16 Impact Factor
  • Hasenah Ali, P J Houghton, Amala Soumyanath
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    ABSTRACT: Extracts of six selected Malaysian plants with a reputation of usefulness in treating diabetes were examined for alpha-amylase inhibition using an in vitro model. Inhibitory activity studied by two different protocols (with and without pre-incubation) showed that Phyllanthus amarus hexane extract had alpha-amylase inhibitory properties. Hexane and dichloromethane extracts of Anacardium occidentale, Lagerstroemia speciosa, Averrhoa bilimbiPithecellobium jiringa and Parkia speciosa were not active when tested without pre-incubation. Extraction and fractionation of Phyllanthus amarus hexane extract led to the isolation of dotriacontanyl docosanoate, triacontanol and a mixture of oleanolic acid and ursolic acid. Dotriacontanyl docosanoate and the mixture of oleanolic acid and ursolic acid are reported from this plant species for the first time. All compounds were tested in the alpha-amylase inhibition assay and the results revealed that the oleanolic acid and ursolic acid (2:1) mixture was a potent alpha-amylase inhibitor with IC(50)=2.01 microg/ml (4.41 microM) and that it contributes significantly to the alpha-amylase inhibition activity of the extract. Three pure pentacyclic triterpenoids, oleanolic acid, ursolic acid and lupeol were shown to inhibit alpha-amylase.
    Journal of Ethnopharmacology 11/2006; 107(3):449-55. DOI:10.1016/j.jep.2006.04.004 · 2.94 Impact Factor
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    ABSTRACT: Piperine, the major alkaloid of black pepper (Piper nigrum L.; Piperaceae), stimulates melanocyte proliferation and dendrite formation in vitro. This property renders it a potential treatment for the skin depigmentation disorder vitiligo. However, piperine does not stimulate melanin synthesis in vitro, and treatments based on this compound may therefore be more effective with concomitant exposure of the skin to ultraviolet (UV) radiation or sunlight. The present study investigated the effect of UVA and simulated solar radiation (SSR) on the chemical stability of piperine, its melanocyte stimulatory effects and its ability to bind protein and DNA. Chromatographic and spectroscopic analysis confirmed the anticipated photoisomerization of irradiated piperine and showed the absence of any hydrolysis to piperinic acid. Isomerization resulted in the loss of ability to stimulate proliferation of a mouse melanocyte cell line, and to bind to human serum albumin. There was no evidence of DNA binding by piperine either before or after irradiation, showing the absence of photoadduct formation by either piperine or its geometric isomers. This is unlike the situation with psoralens, which form DNA adducts when administered with UVA in treating skin diseases. The present study suggests that exposure to bright sunlight should be avoided both during active application of piperine to the skin and in the storage of piperine products. If UVA radiation is used with piperine in the treatment of vitiligo, application of the compound and irradiation should be staggered to minimize photoisomerization. This approach is shown to effectively induce pigmentation in a sparsely pigmented mouse strain.
    Photochemistry and Photobiology 11/2006; 82(6):1541-8. DOI:10.1111/j.1751-1097.2006.tb09809.x · 2.68 Impact Factor
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    ABSTRACT: Axonal regeneration is important for functional recovery following nerve damage. Centella asiatica Urban herb, also known as Hydrocotyle asiatica L., has been used in Ayurvedic medicine for centuries as a nerve tonic. Here, we show that Centella asiatica ethanolic extract (100 microg mL-1) elicits a marked increase in neurite outgrowth in human SH-SY5Y cells in the presence of nerve growth factor (NGF). However, a water extract of Centella was ineffective at 100 microg mL-1. Sub-fractions of Centella ethanolic extract, obtained through silica-gel chromatography, were tested (100 microg mL-1) for neurite elongation in the presence of NGF. Greatest activity was found with a non-polar fraction (GKF4). Relatively polar fractions (GKF10 to GKF13) also showed activity, albeit less than GKF4. Thus, Centella contains more than one active component. Asiatic acid (AA), a triterpenoid compound found in Centella ethanolic extract and GKF4, showed marked activity at 1 microM (microg mL-1). AA was not present in GKF10 to GKF13, further indicating that other active components must be present. Neurite elongation by AA was completely blocked by the extracellular-signal-regulated kinase (ERK) pathway inhibitor PD 098059 (10 microM). Male Sprague-Dawley rats given Centella ethanolic extract in their drinking water (300-330 mg kg-1 daily) demonstrated more rapid functional recovery and increased axonal regeneration (larger calibre axons and greater numbers of myelinated axons) compared with controls, indicating that the axons grew at a faster rate. Taken together, our findings indicate that components in Centella ethanolic extract may be useful for accelerating repair of damaged neurons.
    Journal of Pharmacy and Pharmacology 10/2005; 57(9):1221-9. DOI:10.1211/jpp.57.9.0018 · 2.16 Impact Factor

Publication Stats

274 Citations
26.65 Total Impact Points

Institutions

  • 2005–2015
    • Oregon Health and Science University
      • Department of Neurology
      Portland, Oregon, United States
  • 2008
    • ICL
      Londinium, England, United Kingdom
  • 2006–2007
    • King's College London
      • Department of Pharmacy
      Londinium, England, United Kingdom