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Blood-Brain Barrier Permeability of Asiaticoside, Madecassoside and Asiatic Acid in Porcine Brain Endothelial Cell Model

Hanapi NA, Mohamad Arshad AS, Abdullah JM, Tengku Muhammad TS, Yusof SR

J Pharm Sci, 2021 02;110(2):698-706.
PMID: 32949562 DOI: 10.1016/j.xphs.2020.09.015

Neurotherapeutic potentials of Centella asiatica and its reputation to boost memory, prevent cognitive deficits and improve brain functions are widely acknowledged. The plant's bioactive compounds, i.e. asiaticoside, madecassoside and asiatic acid were reported to have central nervous system (CNS) actions, particularly in protecting the brain against neurodegenerative disorders. Hence, it is important for these compounds to cross the blood-brain barrier (BBB) to be clinically effective therapeutics. This study aimed to explore the capability of asiaticoside, madecassoside and asiatic acid to cross the BBB using in vitro BBB model from primary porcine brain endothelial cells (PBECs). Our findings showed that asiaticoside, madecassoside and asiatic acid are highly BBB permeable with apparent permeability (Papp) of 70.61 ± 6.60, 53.31 ± 12.55 and 50.94 ± 10.91 × 10-6 cm/s respectively. No evidence of cytotoxicity and tight junction disruption of the PBECs were observed in the presence of these compounds. Asiatic acid showed cytoprotective effect towards the PBECs against oxidative stress. This study reported for the first time that Centella asiatica compounds demonstrated high capability to cross the BBB, comparable to central nervous system drugs, and therefore warrant further development as therapeutics for the treatment of neurodegenerative diseases.

Matched MeSH terms: Centella
Oral administration of Centella asiatica (L.) Urb leave aqueous extract ameliorates cerebral oxidative stress, inflammation, and apoptosis in male rats with type-2 diabetes

Giribabu N, Karim K, Kilari EK, Nelli SR, Salleh N

Inflammopharmacology, 2020 Dec;28(6):1599-1622.
PMID: 32588370 DOI: 10.1007/s10787-020-00733-3

Centella asiatica is claimed to have a neuroprotective effect; however, its ability to protect the cerebrum against damage in diabetes has never been identified. The aims were to identify the possibility that C. asiatica ameliorates inflammation, oxidative stress, and apoptosis in the cerebrum in diabetes. C. asiatica leave aqueous extract (C. asiatica) (50, 100, and 200 mg/kg/b.w.) were given to diabetic rats for 28 days. Changes in rats' body weight, food and water intakes, and insulin and FBG levels were monitored. Following sacrificed, cerebrum was harvested and subjected for histological, biochemical, and molecular biological analyses. The results revealed treatment with C. asiatica was able to ameliorate the loss in body weight, the increase in food and water intakes, the decrease in insulin, and the increase in FBG levels in diabetic rats. Additionally, histopathological changes in the cerebrum and levels of p38, ERK, JNK, cytosolic Nrf2, Keap-1, LPO, RAGE, and AGE levels decreased; however, PI3K, AKT, IR, IRS, GLUT-1, nuclear Nrf2, Nqo-1, Ho-1, and anti-oxidative enzymes (SOD, CAT, and GPx) levels increased in diabetic rats receiving C. asiatica. Furthermore, C. asiatica treatment also caused cerebral inflammation and apoptosis to decrease as indicated by decreased inflammatory markers (cytosolic NF-κB p65, p-Ikkβ, Ikkβ, iNOS, COX-2, TNF-α, IL-6, and IL-1β), decreased pro-apoptosis markers (Casp-3, 9, and Bax), but increased anti-apoptosis marker, Bcl-2. Activity level of Na+/K+, Mg2+, and Ca2+-ATPases in the cerebrum also increased by C. asiatica treatment. Conclusions: C. asiatica treatment helps to prevent cerebral damage and maintain near normal cerebral function in diabetes.

Matched MeSH terms: Centella/chemistry*
Fulltext Combining In Silico and In Vitro Studies to Evaluate the Acetylcholinesterase Inhibitory Profile of Different Accessions and the Biomarker Triterpenes of Centella asiatica

Jusril NA, Muhamad Juhari ANN, Abu Bakar SI, Md Saad WM, Adenan MI

Molecules, 2020 Jul 24;25(15).
PMID: 32721993 DOI: 10.3390/molecules25153353

Alzheimer's disease (AD) is a neurodegenerative disease and the most cause of dementia in elderly adults. Acetylcholinesterase (AChE) is an important beneficial target for AD to control cholinergic signaling deficit. Centella asiatica (CA) has proven to be rich with active ingredients for memory enhancement. In the present study, the chemical profiling of three accession extracts of CA namely SECA-K017, SECA-K018, and, SECA-K019 were performed using high-performance liquid chromatography (HPLC). Four biomarker triterpene compounds were detected in all CA accessions. Quantitative analysis reveals that madecassoside was the highest triterpene in all the CA accessions. The biomarker compounds and the ethanolic extracts of three accessions were investigated for their acetylcholinesterase (AChE) inhibitory activity using Ellman's spectrophotometer method. The inhibitory activity of the triterpenes and accession extracts was compared with the standard AChE inhibitor eserine. The results from the in vitro study showed that the triterpene compounds exhibited an AChE inhibitory activity with the half-maximal inhibitory concentration (IC50) values between 15.05 ± 0.05 and 59.13 ± 0.18 µg/mL. Asiatic acid was found to possess strong AChE inhibitory activity followed by madecassic acid. Among the CA accession extracts, SECA-K017 and SECA-K018 demonstrated a moderate AChE inhibitory activity with an IC50 value of 481.5 ± 0.13 and 763.5 ± 0.16 µg/mL, respectively from the in silico docking studies, it is observed that asiatic acid and madecassic acid showed very good interactions with the active sites and fulfilled docking parameters against AChE. The present study suggested that asiatic acid and madecassic acid in the CA accessions could be responsible for the AChE inhibitory action and could be used as markers to guide further studies on CA as potential natural products for the treatment of AD.

Matched MeSH terms: Centella/chemistry*
Fulltext Centella asiatica (L.)-Neurodifferentiated Mesenchymal Stem Cells Promote the Regeneration of Peripheral Nerve

Hussin HM, Lawi MM, Haflah NHM, Kassim AYM, Idrus RBH, Lokanathan Y

Tissue Eng Regen Med, 2020 04;17(2):237-251.
PMID: 32036567 DOI: 10.1007/s13770-019-00235-6

BACKGROUND: Centella asiatica (L.) is a plant with neuroprotective and neuroregenerative properties; however, its effects on the neurodifferentiation of mesenchymal stem cells (MSCs) and on peripheral nerve injury are poorly explored. This study aimed to investigate the effects of C. asiatica (L.)-neurodifferentiated MSCs on the regeneration of peripheral nerve in a critical-size defect animal model.
METHODS: Nerve conduit was developed using decellularised artery seeded with C. asiatica-neurodifferentiated MSCs (ndMSCs). A 1.5 cm sciatic nerve injury in Sprague-Dawley rat was bridged with reversed autograft (RA) (n = 3, the gold standard treatment), MSC-seeded conduit (MC) (n = 4) or ndMSC-seeded conduit (NC) (n = 4). Pinch test and nerve conduction study were performed every 2 weeks for a total of 12 weeks. At the 12th week, the conduits were examined by histology and transmission electron microscopy.
RESULTS: NC implantation improved the rats' sensory sensitivity in a similar manner to RA. At the 12th week, nerve conduction velocity was the highest in NC compared with that of RA and MC. Axonal regeneration was enhanced in NC and RA as shown by the expression of myelin basic protein (MBP). The average number of myelinated axons was significantly higher in NC than in MC but significantly lower than in RA. The myelin sheath thickness was higher in NC than in MC but lower than in RA.
CONCLUSION: NC showed promising effects on nerve regeneration and functional restoration similar to those of RA. These findings revealed the neuroregenerative properties of C. asiatica and its potential as an alternative strategy for the treatment of critical size nerve defect.

Matched MeSH terms: Centella
Fulltext Standardised extracts of Moringa Oleifera and Centella Asiatica enhanced the antioxidant activity, learning and memory effects by inhibiting acetylcholinesterase activity in D-galactose induced ageing rats

Hisyam Jamari, Mohd Salleh Rofiee, Richard James Johari, Mohd Zaki Salleh, Teh, Lay Kek

Pertanika Journal of Science & Technology, 2020;28(1):293-310.
MyJurnal

The potential of Moringa oleifera Lam. (Moringaceae) and Centella asiatica (L.) Urban (Apiaceae) extracts (TGT-PRIMAAGE) in slowing the decline of memory and learning activity was investigated using D-galactose-induced ageing rat model. The extracts were profiled and standardised based on markers identified using LC/MS-QTOF. Toxicity study of the extract was done, and the rat did not show any sign of toxicity. The extract was orally administered to the rat and dose dependent (100, 500 and 1000 mg/kg) efficacy were investigated. The rats were subjected to Morris Water Maze whereby 3 parameters were studied (number of entry to platform, latency and novel object recognition). Plasma was collected for the determination of catalase (CAT) activity and levels of malondialdehyde (MDA) and advanced glycation end products (AGEs). The activity of acetylcholinesterase (AChE), level of acetylcholine (ACh) and lipid peroxidation (LPO) were measured using the brain lysates. Significant improvement (p < 0.05) was seen in the memory and learning abilities in the aged rats that received medium and high dose of TGT-PRIMAAGE, and tocotrienol. Rats treated with TGT-PRIMAAGE had also shown improved CAT activity and resulted in reduced LPO. The level of ACh was found increased in parallel with the reduced AChE activity. The capabilities of learning and memory of the TGT-PRIMAAGE treated rats were enhanced via inhibition of AChE activity and subsequently increased level of ACh.

Matched MeSH terms: Centella
Fulltext Microbiological and physical properties of pennywort (Centella asiatica) leaves using pulsed light technology

Siti Zaharah, R., Noranizan, M., Son, R., Roselina, K., Yusof, N. L., Koh, P. C., et al.

International Food Research Journal, 2020;27(1):16-27.
MyJurnal

Pennywort (Centella asiatica) is a herbaceous vegetable commonly consumed raw as ‘ulam’ or salad. Consumption of raw leafy green vegetables is one of the pathogenic mechanisms that could cause foodborne outbreaks. The aim of the present work was therefore to investigate the effect of pulsed light (PL) treatment at fluences of 1.5, 4.2, 6.9, 9.6, and 12.3 J/cm² on the microbiological and physical quality of pennywort stored at 4 ± 1°C. Escherichia coli (E. coli) were inoculated onto the pennywort leaves before being exposed to PL and viewed using scanning electron microscopy (SEM). PL fluences of 6.9, 9.6, and 12.3 J/cm² significantly reduced the microbial count; however, the highest inactivation was obtained by using fluences of 9.6 and 12.3 J/cm². The color of pennywort was not significantly affected by PL treatment applied at lower fluences of 1.5, 4.2, and 6.9 J/cm²; however, at higher fluence, 9.6 and 12.3 J/cm², the color was affected. PL at 1.5, 4.2, 6.9, and 9.6 J/cm² was able to retain the texture appearance of the leaves. To conclude, PL at 6.9 J/cm² showed the best fluence to reduce total aerobic mesophilic count while retaining the physical properties of pennywort leaves and extend the shelf life to about four days. The inactivation of E. coli population was significantly higher at PL fluence of 6.9 J/cm². It was observed that PL caused the destruction to the surface of E. coli’s cell membrane. The reductions of samples inoculated with E. coli were better than those achieved in native microbiota. Furthermore, the present work also demonstrated that PL treatment was able to reduce the microbial count on pennywort leaves.

Matched MeSH terms: Centella
Fulltext A Review of Malaysian Herbal Plants and Their Active Constituents with Potential Therapeutic Applications in Sepsis

Liew KY, Hafiz MF, Chong YJ, Harith HH, Israf DA, Tham CL

Evid Based Complement Alternat Med, 2020;2020:8257817.
PMID: 33193799 DOI: 10.1155/2020/8257817

Sepsis refers to organ failure due to uncontrolled body immune responses towards infection. The systemic inflammatory response triggered by pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS) from Gram-negative bacteria, is accompanied by the release of various proinflammatory mediators that can lead to organ damage. The progression to septic shock is even more life-threatening due to hypotension. Thus, sepsis is a leading cause of death and morbidity globally. However, current therapies are mainly symptomatic treatment and rely on the use of antibiotics. The lack of a specific treatment demands exploration of new drugs. Malaysian herbal plants have a long history of usage for medicinal purposes. A total of 64 Malaysian plants commonly used in the herbal industry have been published in Malaysian Herbal Monograph 2015 and Globinmed website (http://www.globinmed.com/). An extensive bibliographic search in databases such as PubMed, ScienceDirect, and Scopus revealed that seven of these plants have antisepsis properties, as evidenced by the therapeutic effect of their extracts or isolated compounds against sepsis-associated inflammatory responses or conditions in in vitro or/and in vivo studies. These include Andrographis paniculata, Zingiber officinale, Curcuma longa, Piper nigrum, Syzygium aromaticum, Momordica charantia, and Centella asiatica. Among these, Z. officinale is the most widely studied plant and seems to have the highest potential for future therapeutic applications in sepsis. Although both extracts as well as active constituents from these herbal plants have demonstrated potential antisepsis activity, the activity might be primarily contributed by the active constituent(s) from each of these plants, which are andrographolide (A. paniculata), 6-gingerol and zingerone (Z. officinale), curcumin (C. longa), piperine and pellitorine (P. nigrum), biflorin (S. aromaticum), and asiaticoside, asiatic acid, and madecassoside (C. asiatica). These active constituents have shown great antisepsis effects, and further investigations into their clinical therapeutic potential may be worthwhile.

Matched MeSH terms: Centella
Cardiovascular Protective Effects of Centella asiatica and Its Triterpenes: A Review

Razali NNM, Ng CT, Fong LY

Planta Med, 2019 Nov;85(16):1203-1215.
PMID: 31539918 DOI: 10.1055/a-1008-6138

Centella asiatica, a triterpene-rich medicinal herb, is traditionally used to treat various types of diseases including neurological, dermatological, and metabolic diseases. A few articles have previously reviewed a broad range of pharmacological activities of C. asiatica, but none of these reviews focuses on the use of C. asiatica in cardiovascular diseases. This review aims to summarize recent findings on protective effects of C. asiatica and its active constituents (asiatic acid, asiaticoside, madecassic acid, and madecassoside) in cardiovascular diseases. In addition, their beneficial effects on conditions associated with cardiovascular diseases were also reviewed. Articles were retrieved from electronic databases such as PubMed and Google Scholar using keywords "Centella asiatica," "asiatic acid," "asiaticoside," "madecassic acid," and "madecassoside." The articles published between 2004 and 2018 that are related to the aforementioned topics were selected. A few clinical studies published beyond this period were also included. The results showed that C. asiatica and its active compounds possess potential therapeutic effects in cardiovascular diseases and cardiovascular disease-related conditions, as evidenced by numerous in silico, in vitro, in vivo, and clinical studies. C. asiatica and its triterpenes have been reported to exhibit cardioprotective, anti-atherosclerotic, antihypertensive, antihyperlipidemic, antidiabetic, antioxidant, and anti-inflammatory activities. In conclusion, more clinical and pharmacokinetic studies are needed to support the use of C. asiatica and its triterpenes as therapeutic agents for cardiovascular diseases. Besides, elucidation of the molecular pathways modulated by C. asiatica and its active constituents will help to understand the mechanisms underlying the cardioprotective action of C. asiatica.

Matched MeSH terms: Centella/chemistry*
Fulltext Pharmacological properties of Centella asiatica hydrogel in accelerating wound healing in rabbits

Sh Ahmed A, Taher M, Mandal UK, Jaffri JM, Susanti D, Mahmood S, et al.

BMC Complement Altern Med, 2019 Aug 14;19(1):213.
PMID: 31412845 DOI: 10.1186/s12906-019-2625-2

BACKGROUND: Various extracts of Centella asiatica (Apiaceae) and its active constituent, asiaticoside, have been reported to possess wound healing property when assessed using various in vivo and in vitro models. In an attempt to develop a formulation with accelerated wound healing effect, the present study was performed to examine in vivo efficacy of asiaticoside-rich hydrogel formulation in rabbits.
METHODS: Asiaticoside-rich fraction was prepared from C. asiatica aerial part and then incorporated into polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogel. The hydrogel was subjected to wound healing investigation using the in vivo incision model.
RESULTS: The results obtained demonstrated that: i) the hydrogel formulation did not cause any signs of irritation on the rabbits' skin and; ii) enhanced wound healing 15% faster than the commercial cream and > 40% faster than the untreated wounds. The skin healing process was seen in all wounds marked by formation of a thick epithelial layer, keratin, and moderate formation of granulation tissues, fibroblasts and collagen with no fibrinoid necrosis detected.
CONCLUSION: The asiaticoside-rich hydrogel developed using the freeze-thaw method was effective in accelerating wound healing in rabbits.

Matched MeSH terms: Centella/chemistry*
Fulltext Centella asiatica Protects d-Galactose/AlCl3 Mediated Alzheimer's Disease-Like Rats via PP2A/GSK-3β Signaling Pathway in Their Hippocampus

Chiroma SM, Baharuldin MTH, Mat Taib CN, Amom Z, Jagadeesan S, Ilham Adenan M, et al.

Int J Mol Sci, 2019 Apr 16;20(8).
PMID: 31014012 DOI: 10.3390/ijms20081871

Alzheimer's disease (AD) is a progressive neurodegenerative disorder more prevalent among the elderly population. AD is characterised clinically by a progressive decline in cognitive functions and pathologically by the presence of neurofibrillary tangles (NFTs), deposition of beta-amyloid (Aβ) plaque and synaptic dysfunction in the brain. Centella asiatica (CA) is a valuable herb being used widely in African, Ayurvedic, and Chinese traditional medicine to reverse cognitive impairment and to enhance cognitive functions. This study aimed to evaluate the effectiveness of CA in preventing d-galactose/aluminium chloride (d-gal/AlCl3) induced AD-like pathologies and the underlying mechanisms of action were further investigated for the first time. Results showed that co-administration of CA to d-gal/AlCl3 induced AD-like rat models significantly increased the levels of protein phosphatase 2 (PP2A) and decreased the levels of glycogen synthase kinase-3 beta (GSK-3β). It was further observed that, CA increased the expression of mRNA of Bcl-2, while there was minimal effect on the expression of caspase 3 mRNA. The results also showed that, CA prevented morphological aberrations in the connus ammonis 3 (CA 3) sub-region of the rat's hippocampus. The results clearly demonstrated for the first time that CA could alleviate d-gal/AlCl3 induced AD-like pathologies in rats via inhibition of hyperphosphorylated tau (P-tau) bio-synthetic proteins, anti-apoptosis and maintenance of cytoarchitecture.

Matched MeSH terms: Centella/metabolism; Centella/chemistry*
Fulltext Differential expression of entorhinal cortex and hippocampal subfields α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors enhanced learning and memory of rats following administration of Centella asiatica

Wong JH, Muthuraju S, Reza F, Senik MH, Zhang J, Mohd Yusuf Yeo NAB, et al.

Biomed Pharmacother, 2019 Feb;110:168-180.
PMID: 30469081 DOI: 10.1016/j.biopha.2018.11.044

Centella asiatica (CA) is a widely used traditional herb, notably for its cognitive enhancing effect and potential to increase synaptogenesis. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) mediate fast excitatory neurotransmission with key roles in long-term potentiation which is believed to be the cellular mechanism of learning and memory. Improved learning and memory can be an indication to the surface expression level of these receptors. Our previous study demonstrated that administration of CA extract improved learning and memory and enhanced expression of AMPAR GluA1 subunit while exerting no significant effects on GABAA receptors of the hippocampus in rats. Hence, to further elucidate the effects of CA, this study investigated the effects of CA extract in recognition memory and spatial memory, and its effects on AMPAR GluA1 and GluA2 subunit and NMDAR GluN2 A and GluN2B subunit expression in the entorhinal cortex (EC) and hippocampal subfields CA1 and CA3. The animals were administered with saline, 100 mg/kg, 300 mg/kg, and 600 mg/kg of CA extract through oral gavage for 14 days, followed by behavioural analysis through Open Field Test (OFT), Novel Object Recognition Task (NORT), and Morris Water Maze (MWM) and lastly morphological and immunohistochemical analysis of the surface expression of AMPAR and NMDAR subunits were performed. The results showed that 14 days of administration of 600 mg/kg of CA extract significantly improved memory assessed through NORT while 300 mg/kg of CA extract significantly improved memory of the animals assessed through MWM. Immunohistochemical analysis revealed differential modulation effects on the expressions of receptor subunits across CA1, CA3 and EC. The CA extract at the highest dose (600 mg/kg) significantly enhanced the expression of AMPAR subunit GluA1 and GluA2 in CA1, CA3 and EC, and NMDAR subunit GluN2B in CA1 and CA3 compared to control. At 300 mg/kg, CA significantly increased expression of AMPAR GluA1 in CA1 and EC, and GluA2 in CA1, CA3 and EC while 100 mg/kg of CA significantly increased expression of only AMPAR subunit GluA2 in CA3 and EC. Expression of NMDAR subunit GluN2 A was significantly reduced in the CA3 (at 100, 300, and 600 mg/kg) while no significant changes of subunit expression was observed in CA1 and EC compared to control. The results suggest that the enhanced learning and memory observed in animals administered with CA was mainly mediated through increased expression of AMPAR GluA1 and GluA2 subunits and differential expression of NMDAR GluN2 A and GluN2B subunits in the hippocampal subfields and EC. With these findings, the study revealed a new aspect of cognitive enhancing effect of CA and its therapeutic potentials through modulating receptor subunit expression.

Matched MeSH terms: Centella*
Combined extract of Moringa oleifera and Centella asiatica modulates oxidative stress and senescence in hydrogen peroxide-induced human dermal fibroblasts

Abdul Hisam EE, Rofiee MS, Khalid AM, Jalaluddin AF, Mohamad Yusof MI, Idris MH, et al.

Turk J Biol, 2018;42(1):33-44.
PMID: 30814868 DOI: 10.3906/biy-1708-23

Moringa oleifera Lam. and Centella asiatica (L.) Urb. leaves have been previously reported to exhibit antioxidant activity. The objective of the present study is to determine the in vitro antioxidant activity of the combined extracts of M. oleifera and C. asiatica (TGT-PRIMAAGE) and its effect on hydrogen peroxide (H 2O2)-induced oxidative stress in human dermal fibroblasts. TGTPRIMAAGE acted on the mechanism of hydrogen transfer as it showed scavenging activity in the DPPH assay. This is due to the presence of phenolics and flavonoids in TGT-PRIMAAGE. TGT-PRIMAAGE effectively reduced cellular generation of reactive oxygen species induced by H O2. The activities of superoxide dismutase and catalase were also increased in cells treated with TGT-PRIMAAGE. 2 Treatment with TGT-PRIMAAGE showed significant reduction (P < 0.05) in the number of senescent cells. Significant reduction (P < 0.05) of malondialdehyde was also seen in cells treated with TGT-PRIMAAGE. The p53 protein level was reduced in TGT-PRIMAAGEtreated cells, which indicates its potential in protecting the cells from oxidative stress induced by H2O2.

Matched MeSH terms: Centella
Fulltext Effects of Centella asiatica (L.) Urb. on cognitive function and mood related outcomes: A Systematic Review and Meta-analysis

Puttarak P, Dilokthornsakul P, Saokaew S, Dhippayom T, Kongkaew C, Sruamsiri R, et al.

Sci Rep, 2017 09 06;7(1):10646.
PMID: 28878245 DOI: 10.1038/s41598-017-09823-9

Centella asiatica (L.) Urb. has been used as an herbal brain tonic for mental disorders and enhancing memory, but no review of the overall evidence of C. asiatica and cognitive function has been conducted. This study aims to determine the effects of C. asiatica on cognitive function and its related properties. The current systematic review includes five randomized controlled trials (RCTs) conducted to determine the effect of C. asiatica alone and six RCTs conducted to determine the effect of C. asiatica-containing products. Meta-analysis indicated that there are no significant differences in all cognitive function domains of C. asiatica when compared to placebo. However, it could improve mood by increasing alert scores [SMD: 0.71 (95% CI; 0.01 to 1.41); I2 = 30.5%] and decreasing anger scores at 1 hour after treatment [SMD: -0.81 (95%CI; -1.51 to -0.09); I2 = 36.6%]. None of the studies reported adverse effects of C. asiatica. In conclusion, there is not strong evidence to support the use of C. asiatica for cognitive function improvement in each cognitive domain. C. asiatica could improve alertness and relieve anger. However, some limitations should be aware including dose regimen, plant preparation, standardization, and product variation. Future well-designed clinical trials using suitable doses of standardized C. asiatica are still needed.

Matched MeSH terms: Centella/chemistry*
Fulltext The modified Gompertz model demonstrates a variable growth rate between two Centella asiatica phenotypes

Hussein, S., Halmi, M.I.E., Ling, A.P.K.

Journal of Biochemistry, Microbiology and Biotechnology, 2017;5(1):18-20.
MyJurnal

Centella asiatica, a weakly aromatic plant that flourishes in wet tropical and sub-tropical areas as
a medicinal species since ancient times. It contained important terpenoids that impart important
medicinal values. Currently, studies on the terpenoid content of various Centella asiatica
phenotypes have shown not only variable content but variable growth rates of different
phenotypes that can affect future selection of phenotypes. The use of mathematical growth
modelling can reveal important growth constants and discriminate between faster and slower
growth phenotypes. Two Centella asiatica phenotypes from South Africa is modelled using the
modified Gompertz model and the results showed that the C. asiatica Type-1 exhibited a faster
growth rates and a shorter lag period at 0.152 day-1 and 2.313 day than another phenotype; C.
asiatica Type 2 with a growth rate and a lag period of 0.067 day-1 and 3.363 day, respectively.
The data indicates that different phenotypes of C. asiatica can have different growth rates and
lag period and this can be important for selection of phenotypes to be used as the best bioactive
peptides producer.

Matched MeSH terms: Centella
Phytoremediation of iron from red soil of tropical region by using Centella asiatica

Bhat IU, Mauris EN, Khanam Z

Int J Phytoremediation, 2016 Sep;18(9):918-23.
PMID: 26940261 DOI: 10.1080/15226514.2016.1156637

The accumulation and removal efficiency of Fe by Centella asiatica was carried out at various Fe concentrations in soil treatments (0, 50, 100, 150 and 200 mg Fe/kg soil). Iron accumulation in different parts of C. asiatica (leaf, stem and root) was analyzed by atomic absorption spectrophotometer (AAS). Factorial experiment with a completely randomized design and Duncan's test were used for data analyses. The results revealed that C. asiatica have the ability to uptake and accumulate Fe significantly (p 1 and <1, respectively, further supporting its metal hyperaccumulator properties.

Matched MeSH terms: Centella/metabolism*
Metabolic alteration in obese diabetes rats upon treatment with Centella asiatica extract

Maulidiani, Abas F, Khatib A, Perumal V, Suppaiah V, Ismail A, et al.

J Ethnopharmacol, 2016 Mar 2;180:60-9.
PMID: 26775274 DOI: 10.1016/j.jep.2016.01.001

'Pegaga' is a traditional Malay remedy for a wide range of complaints. Among the 'pegaga', Centella asiatica has been used as a remedy for diabetes mellitus. Thus, we decided to validate this claim by evaluating the in vivo antidiabetic property of C. asiatica (CA) on T2DM rat model using the holistic (1)H NMR-based metabolomics approach.

Matched MeSH terms: Centella
Effects of metal-contaminated soils on the accumulation of heavy metals in gotu kola (Centella asiatica) and the potential health risks: a study in Peninsular Malaysia

Ong GH, Wong LS, Tan AL, Yap CK

Environ Monit Assess, 2016 Jan;188(1):40.
PMID: 26687083 DOI: 10.1007/s10661-015-5042-0

Centella asiatica is a commonly used medicinal plant in Malaysia. As heavy metal accumulation in medicinal plants which are highly consumed by human is a serious issue, thus the assessment of heavy metals in C. asiatica is important for the safety of consumers. In this study, the heavy metal accumulation in C. asiatica and the potential health risks were investigated. Samples of C. asiatica and surface soils were collected from nine different sites around Peninsular Malaysia. The concentration of six heavy metals namely Cd, Cu, Ni, Fe, Pb and Zn were determined by air-acetylene flame atomic absorption spectrophotometer (AAS). The degree of anthropogenic influence was assessed by calculating the enrichment factor (EF) and index of geoaccumulation (Igeo). The heavy metal uptake into the plant was estimated through the calculation of translocation factor (TF), bioconcentration factor (BCF) and correlation study. Estimated daily intakes (EDI) and target hazard quotients (THQ) were used to determine the potential health risk of consuming C. asiatica. The results showed that the overall surface soil was polluted by Cd, Cu and Pb, while the uptake of Zn and Ni by the plants was high. The value of EDI and THQ showed that the potential of Pb toxicity in C. asiatica was high as well. As heavy metal accumulation was confirmed in C. asiatica, daily consumption of the plant derived from polluted sites in Malaysia was not recommended.

Matched MeSH terms: Centella/chemistry*
Fulltext Recent Updates in Neuroprotective and Neuroregenerative Potential of Centella asiatica

Lokanathan Y, Omar N, Ahmad Puzi NN, Saim A, Hj Idrus R

Malays J Med Sci, 2016 Jan;23(1):4-14.
PMID: 27540320 MyJurnal

Centella asiatica, locally well known in Malaysia as pegaga, is a traditional herb that has been used widely in Ayurvedic medicine, traditional Chinese medicine, and in the traditional medicine of other Southeast Asian countries including Malaysia. Although consumption of the plant is indicated for various illnesses, its potential neuroprotective properties have been well studied and documented. In addition to past studies, recent studies also discovered and/or reconfirmed that C. asiatica acts as an antioxidant, reducing the effect of oxidative stress in vitro and in vivo. At the in vitro level, C. asiatica promotes dendrite arborisation and elongation, and also protects the neurons from apoptosis. In vivo studies have shown that the whole extract and also individual compounds of C. asiatica have a protective effect against various neurological diseases. Most of the in vivo studies on neuroprotective effects have focused on Alzheimer's disease, Parkinson's disease, learning and memory enhancement, neurotoxicity and other mental illnesses such as depression and anxiety, and epilepsy. Recent studies have embarked on finding the molecular mechanism of neuroprotection by C. asiatica extract. However, the capability of C. asiatica in enhancing neuroregeneration has not been studied much and is limited to the regeneration of crushed sciatic nerves and protection from neuronal injury in hypoxia conditions. More studies are still needed to identify the compounds and the mechanism of action of C. asiatica that are particularly involved in neuroprotection and neuroregeneration. Furthermore, the extraction method, biochemical profile and dosage information of the C. asiatica extract need to be standardised to enhance the economic value of this traditional herb and to accelerate the entry of C. asiatica extracts into modern medicine.

Matched MeSH terms: Centella
From Plant Extract to a cDNA Encoding a Glucosyltransferase Candidate: Proteomics and Transcriptomics as Tools to Help Elucidate Saponin Biosynthesis in Centella asiatica

de Costa F, Barber CJ, Reed DW, Covello PS

Methods Mol Biol, 2016;1405:43-8.
PMID: 26843164 DOI: 10.1007/978-1-4939-3393-8_5

Centella asiatica (L.) Urban (Apiaceae), a small annual plant that grows in India, Sri Lanka, Malaysia, and other parts of Asia, is well-known as a medicinal herb with a long history of therapeutic uses. The bioactive compounds present in C. asiatica leaves include ursane-type triterpene sapogenins and saponins-asiatic acid, madecassic acid, asiaticoside, and madecassoside. Various bioactivities have been shown for these compounds, although most of the steps in the biosynthesis of triterpene saponins, including glycosylation, remain uncharacterized at the molecular level. This chapter describes an approach that integrates partial enzyme purification, proteomics methods, and transcriptomics, with the aim of reducing the number of cDNA candidates encoding for a glucosyltransferase involved in saponin biosynthesis and facilitating the elucidation of the pathway in this medicinal plant.

Matched MeSH terms: Centella
Fulltext Molecular characterization of Escherichia coli isolated from different food sources

Cheah, Y.K., Tay, L.W., Aida, A.A., Son, R., Nakaguchi, T., Nishibuchi, M.

International Food Research Journal, 2015;22(1):31-40.
MyJurnal

Escherichia coli and Escherichia coli O157 were identified from “selom” (Oenanthe stolonifera), “pegaga” (Centella asiatica), beef, chicken, lamb, buffalo, “ulam Raja” (Cosmos caudatus) and “tenggek burung” (Euodia redlevi). The bacteria were recovered using chromagenic agar. Isolated Escherichia coli and Escherichia coli 0157 were further characterized by plasmid profiling and enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR). The virulence genes of the isolates (VT1, VT2, LT, ST, eaeA, inV) that produces pathogenic Escherichia coli and 16S rRNA gene were screened by a multiplex PCR assay. The plasmid profiling analysis showed that out of 176 isolates, only 103 isolates contained plasmids. ERIC-PCR analysis generated amplified products in the range of ~150 bp to > 1000 bp categorizing isolates into a total of 52 different profiles. Multiplex PCR showed that 20 (32.3%) of the isolates carried eaeA gene, 6 (9.7%) isolates possessed inV genes, only 1 (1.6%) have VT2 genes and 1 (1.6%) as well carried VT1 genes, 2 (3.2%) of the isolates harboured LT genes, and only 1 (1.6%) isolate possessed ST genes. There were no correlation between plasmid, ERIC-PCR and virulence genes profiles.

Matched MeSH terms: Centella

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