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Pennywort: Centella asiatica (L.) Urban (Apiaceae)
This chapter presents indications, clinical evidence, pre-clinical evidence, mechanisms of action, interactions, and contraindications of Centella (Centella asiatica). Centella is now mainly used for symptoms of chronic venous insufficiency (CVI), including varicose veins, varicose ulcers, diabetic and airline flight microangiopathy. The herb is also used to aid wound healing and treat skin conditions such as burns, scarring, eczema and psoriasis, as a topical application and oral tablets. It is used in cosmetic preparations to reduce the signs of skin ageing. Centella is also taken orally to relieve anxiety and improve cognition. It has traditionally been used for many other conditions including diarrhoea, fever and amenorrhoea. Adverse effects, dosage, and general plant information are included in the chapter. Centella is found in most tropical and subtropical countries growing in swampy areas.
S u m m a r y Safe, effective and inexpensive indigenous remedies are gaining popularity among the people of both urban and rural areas of India. the present paper provides first-hand information on ethnomedicinal plants recorded from agro-forestry systems and home gardens from Mizoram (an Indo-burma hotspot region). Medicinal uses of plants were assessed on the basis of exhaustive interviews with local physicians practising indigenous system of medicine, home garden owners and various tribal groups relying on agroforestry systems of Mizoram, North East (NE) India. the survey results into the uses of 54 ethnomedicinal plant species belonging to 52 genera and 35 families of flowering plants.
Centella asiatica herbs have been prescribed as a traditional medicine for wound healing in China and Southeast Asia for a long time. They contain many kinds of triterpenoid compounds, mainly including glycosides (asiaticoside and madecassoside) and corresponding aglycones (asiatic acid and madecassic acid). To identify which is the major active constituent, a comprehensive and comparative study of these compounds was performed. In vitro, primary human skin fibroblasts, originating from healthy human foreskin samples, were treated with various concentrations of asiaticoside, madecassoside, asiatic acid, and madecassic acid, respectively. Cell proliferation, collagen synthesis, MMP-1/TIMP-1 balance, and TGF-β/Smad signaling pathway were investigated. In vivo, mice were orally administered with the four compounds mentioned above for two weeks after burn injury. The speed and quality of wound healing, as well as TGF-β(1) levels in skin tissues, were examined. Interestingly, in contrast to prevalent postulations, asiaticoside and madecassoside themselves, rather than their corresponding metabolites asiatic acid and madecassic acid, are recognized as the main active constituents of C. asiatica herbs responsible for burn wound healing. Furthermore, madecassoside is more effective than asiaticoside (P = 0.0446 for procollagen type III synthesis in vitro, P = 0.0057 for wound healing speed, and P = 0.0491 for wound healing pattern in vivo, correspondingly).
In South Africa, Centella asiatica. (L.) Urb is used traditionally for the treatment of various diseases. Analyses of the essential oil of this medicinal plant revealed 11 monoterpenoid hydrocarbons (20.20%), nine oxygenated monoterpenoids (5.46%), 14 sesquiterpenoid hydrocarbons (68.80%), five oxygenated sesquiterpenoids (3.90%), and one sulfide sesquiterpenoid (0.76%). α.-Humulene (21.06%), β.-caryophyllene (19.08%), bicyclogermacrene (11.22%), germacrene B (6.29%), and myrcene (6.55%) were the predominant constitutes. The essential oil extract exhibited a broad spectrum of antibacterial activities against Gram-positive (Bacillus subtilis, Staphylococcus aureus.) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Shigella sonnei.) organisms.
Asiaticoside, an active ingredient extracted from Centella asiatica, has been widely used to promote wound healing. In this study, the effects of asiaticoside on proliferation, protein synthesis, and osteogenic differentiation in human periodontal ligament cells (HPDLs) were investigated. HPDLs were treated with asiaticoside at concentrations of 25, 50, and 100 µg/mL. Cell number was determined by MTT assay. The mRNA expression was analyzed by reverse transcription-polymerase chain reaction. Western blot analysis and immunocytochemistry were used to confirm protein synthesis. Osteogenic differentiation was determined by alkaline phosphatase activity, osteoblast marker gene expression, and in vitro mineralization. The results showed that asiaticoside treatment, ranging from 25 to 100 mg/mL, had no effect on cytotoxicity or cell proliferation. When HPDLs were treated with asiaticoside in serum-free medium, dose-dependent increases in the levels of fibronectin and collagen type I mRNA and protein were observed at 72 h. Moreover, asiaticoside attenuated matrix metalloproteinase-1 but enhanced tissue inhibitor of metalloproteinase-1 mRNA expression. The addition of asiaticoside to osteogenic medium resulted in an increase in alkaline phosphatase enzymatic activity, up-regulation of osteoblast marker gene mRNA expression, and enhancement of mineralization by HPDLs. These results suggest the potential application of asiaticoside for enhancing periodontal tissue healing. Copyright © 2012 John Wiley & Sons, Ltd.
Centella asiatica is reputed for its beneficial effects in various neurological disorders. The present investigation was undertaken to evaluate the role of 70% hydro-ethanolic extract of Centella asiatica (CA) on generalized anxiety disorder (GAD) in man. Hamilton's Brief Psychiatric Rating Scale (BPRS) was used to screen the subjects. Thirty-three participants (18 male and 15 female; average age 33 yrs) were medicated with the CA in a fixed dose regime (500 mg/capsule, twice daily, after meal). They were thoroughly investigated using standard questionnaires based on psychological rating scale at baseline (day 0), mid-term (day 30) and final (day 60). The scale also includes a number of direct queries about current levels of experienced stress. The observations revealed that, CA not only significantly (p<0.01) attenuated anxiety related disorders but it also significantly (p<0.01) reduced stress phenomenon and its correlated depression. CA further significantly (p<0.01) improved the willingness for adjustment and cognition. Results indicated that Centella asiatica may be useful in the treatment of GAD and may be used as a promising anxiolytic agent in near future.
Centella asiatica accumulates large quantities of pentacyclic triterpenoid saponins, collectively known as centelloids. These terpenoids include asiaticoside, centelloside, madecassoside, brahmoside, brahminoside, thankuniside, sceffoleoside, centellose, asiatic-, brahmic-, centellic- and madecassic acids. The triterpene saponins are common secondary plant metabolites and are synthesized via the isoprenoid pathway to produce a hydrophobic triterpenoid structure (aglycone) containing a hydrophilic sugar chain (glycone). The biological activity of saponins has been attributed to these characteristics. In planta, the Centella triterpenoids can be regarded as phytoanticipins due to their antimicrobial activities and protective role against attempted pathogen infections. Preparations of C. asiatica are used in traditional and alternative medicine due to the wide spectrum of pharmacological activities associated with these secondary metabolites. Here, the biosynthesis of the centelloid triterpenoids is reviewed; the range of metabolites found in C. asiatica, together with their known biological activities and the chemotype variation in the production of these metabolites due to growth conditions are summarized. These plant-derived pharmacologically active compounds have complex structures, making chemical synthesis an economically uncompetitive option. Production of secondary metabolites by cultured cells provides a particularly important benefit to manipulate and improve the production of desired compounds; thus biotechnological approaches to increase the concentrations of the metabolites are discussed.
Centella asiatica is a medicinal plant that has been in use since prehistoric times. Its active constituents include pentacyclic triterpene derivatives. Studies have been conducted in particular to investigate the madecassosides and asiaticosides. In common with most traditional phytotherapeutic agents, Centella asiatica is used in folk medicine to treat a wide range of indications. In contrast to other medicinal plants, however, Centella asiatica has been subjected to quite extensive experimental and clinical investigations. Studies done in accordance with standardized scientific criteria have shown it to have a positive effect in the treatment of venous insufficiency and striae gravidarum. Centella asiatica also appears to be effective in the treatment of wound healing disturbances. At the present time, clinical studies aimed at investigating the sedative, analgesic, antidepressive, antimicrobial, antiviral and immunomodulatory effects that have been demonstrated experimentally, are still lacking. However, the therapeutic potential of this plant in terms of its efficacy and versatility is such that further detailed research would appear worthwhile.
Centella asiatica (CA) and Rhinacanthus nasutus (RN )have been used for treatment of various illnesses, but the mechanisms of action remain largely unknown. This study focused on the influence of CA and RN extracts on cell-mediated and humoral immune responses. In human peripheral blood mononuclear cells (PBMCs), CA (water extract) and RN (water and ethanol extracts) significantly increased proliferation and the production of IL-2 and TNF-alpha. In contrast, an ethanol extract of CA inhibited human PBMC mitogenesis and the production of IL-2 and TNF-alpha. BALB/c mice treated with CA extracts (100 mg/kg bw) showed higher responses to both primary and secondary antibodies against BSA when compared with non-treated group. Only the secondary antibody response was increased in RN extract-treated mice. The present study revealed immunomodulating activity of CA and RN extracts with regard to both non-specific cellular and humoral immune responses. The data available to date suggest that they may have chemopreventive or anticancer potential.
Objective
To evaluate acute and subacute toxicity of the acetone extract of Centella asiatica (Brahmi).Methods
Toxicity of Centella asiatica was evaluated in Swiss mice after ingestion of the extract during one day (acute model) and during 15 days (subacute model). The Biochemical parameters evaluated included creatinine, calcium, inorganic phosphorous, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assessed using commercial kits.ResultsThe results of the present investigation revealed that the LD50 of the extract is higher than 4000mg/kg and subacute treatment did not shows any change in corporal weight and hematological parameters. However, a change in liver weight but not in hepatic enzymes was observed. This suggested that the liver function is not altered by Centella asiatica. Some changes in the creatinine content were observed but could not be relative with the extract dose.Conclusions
The results suggest that the plant seems to be destitute of toxic effects in mice.
Hydrocotyle sibthorpioides, H. maritima and Centella asiatica were investigated for their ter- penoid constituents. The major component of H. sibthorpioides and H. maritima is trans- β-farnesene. The latter species also elaborates α-terpinene and thymol methyl ether in respectable amount. The sesquiterpenoid constitution of C. asiatica is rather similar to H. maritima. Possible allelopathy between H. sibthorpioides and a liverwort is suggested.
The synergistic antioxidant effects of ethanolic extracts of Centella asiatica (CE), and α-tocopherol have been studied. The types of interactions exhibited by CE and α-tocopherol combined at different ratios were measured using three assays: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical-scavenging capacity, the β-carotene bleaching system and liposome peroxidation assays. Fixed-fraction isobolographic analysis was used to detect any inducement of the antioxidant activity compared with the individual activities of CE and α-tocopherol. Of all synergistic combinations of CE and α-tocopherol, only fraction 2/3 showed the synergistic combination that fits well in three different assays and can be explained by the regeneration of α-tocopherol by CE despite the interaction effect of β-carotene present in the analytical assay. This phenomenon involved complex interactions between CE and α-tocopherol to exhibit different degrees of interactions that eventually increased antioxidant activity.
Objective
Centella asiatica (CeA), a creeper, growing in moist places in India and other Asian countries. Leaves of CeA are used for memory enhancement in Ayurvedic system of medicine, an alternative system of medicine originated from India. In the present study, we have investigated the role of CeA fresh leaf extract treatment on adult rats on dendritic morphology of amygdaloid neurons, one of the regions concerned with learning and memory.
Methods
Adult rats (2.5-month old) were fed with 2, 4 and 6 mL/(day kg) of fresh leaf extract of CeA for 2, 4 and 6 weeks. After the treatment period the rats were killed, brains were removed and amygdaloid neurons were impregnated with silver nitrate (Golgi staining). Such silver impregnated amygdaloid neurons were traced using camera lucida and dendritic branching points (a measure of dendritic arborization) and intersections (a measure of dendritic length) were quantified. These data were compared with those of age matched control rats.
Results
The results showed a significant increase in the dendritic length (intersections) and dendritic branching points in amygdaloid neurons of the rats treated with higher dose [6 mL/(day·kg)] of CeA for longer period of time (i.e. 6 weeks).
Conclusions
Constituents/active principles present CeA fresh leaf extract has neuronal dendritic growth stimulating property; hence it can be used for enhancing neuronal dendrites in stress and other neurodegenerative and memory disorders.
Centella asiatica has long been used for various neurological disturbances in Southeast Asian countries. The present study aims to demonstrate the anxiolytic effect of ECa 233, a standardized extract of C. asiatica containing triterpenoids not less than 80%, in comparison to diazepam.
The test compound was given orally to non-stressed mice and mice subjected to chronic immobilization stress. Anxiolytic effect was assessed by an elevated plus maze (EPM), a dark-light box and an open-field tests.
Anxiolytic effect of ECa 233 was clearly demonstrated in non-stressed mice subjected to acute stress in all behavioral tests employed. In the EPM test, chronically stressed mice showed significant decrease in the number of open arm entries, shortening the time spent in open arms and an increase of the latency to leave the central area, suggesting their release from the stress. In addition, ameliorating effect of ECa 233 was observed on the body weight and serum corticosterone which were adversely affected by immobilization stress. Madecassoside and asiaticoside, equal to their respective contents of the effective doses of ECa 233, exclusively presented anxiolytic effects in EPM, while no distinct effect was observed on the body weight and serum corticosterone.
The present study demonstrated anxiolytic effect of ECa 233 in both acutely and chronically stressed animals. These effects could be mainly accounted by madecassoside and asiaticoside, suggesting a possible use of ECa 233 for the treatment of both acute and chronic anxiety in the pathological state.
Antioxidative activity and total phenolic compounds of root, leaf and petiole of four accessions of Centella asiatica (L.) Urban, namely CA 01, CA 05, CA 08 and CA 11, were evaluated. Antioxidative activity of the extracts was measured using the ferric thiocyanate (FTC) method and thiobarbituric acid (TBA) test. The antioxidative activities were then compared with that of α-tocopherol (natural antioxidant) and butylated hydroxytoulene or BHT (synthetic antioxidant). The results showed that CA 01 and CA 05 had the highest antioxidative activities among the accessions tested. Results also showed that both leaf and root of C. asiatica had high antioxidative activity, which was as good as that of α-tocopherol. The total phenolic content, determined according to the Folin–Ciocalteu method, varied from 3.23 to 11.7 g/100 g dry sample, and showed strong association (r2=0.90) with antioxidative activity. The results suggest that phenolic compounds are the major contributors to the antioxidative activities of C. asiatica.
Plant-derived elements used for pharmacological applications constitute an increasing research field. Centella asiatica is widely used mainly as an extract (TECA). Triterpenic fractions, the primary constituents of Centella asiatica, produce a wide range of preventive and therapeutic effects. The modulation of collagen production and deposition in wound healing is of primary importance. TECA is also used to treat several microcirculatory problems, inflammatory skin conditions (leprosy, lupus, varicose ulcers, eczema, atopic dermatitis, psoriasis) and also intestinal problems, fever, amenorrhea and genitourinary conditions. Cognitive functions, anxiety and mental impairment may be also affected by TECA administration. New applications in neurology include nerve growth factor enhancement and applications in neurological degenerative conditions. Interaction with other products is also indicated in this document. The multiplicity of actions of TECA is associated to six important mechanisms, all inter-connected and modulating each other: 1) edema - and capillary filtration - control; 2) a strong antioxidant power, effective on several forms of oxidative stress associated to inflammation or infections and synergic with other antioxidant products; 3) an anti-inflammatory action; 4) a modulation of the collagen production avoiding slower scarring or faster, hyperthrophic scarring and cheloids; 5) a modulating action of local growth factors; 6) a modulation of angiogenesis. This "status" paper - resulting from an expert meeting held in Cobham, Surrey, indicates most of the therapeutic potential of TECA, still to be explored in further studies. The status paper constitutes the basis for a consensus document on TECA to be developed in the next future. This "status" paper opens a new window on an ancient but still partially unexplored product that may become an important value in prevention and treatment of several pre-clinical and risk conditions and in clinically significant disease both as a single products and in association with other 'natural' products.
Centella asiatica (C. asiatica) is a pharmacological plant in South Asia. It has been demonstrated that C. asiatica extracts containing various pentacyclic triterpenes exert healing effects, especially wound healing and collagen synthesis in skin. However, there are few studies on the effect of C. asiatica extracts on stress-induced premature senescence (SIPS). To determine whether H(2) O(2) -induced senescence is affected by C. asiatica extracts, we performed senescence analysis on cultured human dermal fibroblasts (HDFs). We also analysed whole gene expression level using microarrays and showed that 39 mRNAs are differentially expressed in H(2) O(2) -induced HDFs with and without treatment with C. asiatica extracts. These genes regulate apoptosis, gene silencing, cell growth, transcription, senescence, DNA replication and the spindle checkpoint. Differential expression of FOXM1, E2F2, MCM2, GDF15 and BHLHB2 was confirmed using semi-quantitative PCR. In addition, C. asiatica extracts rescued the H(2) O(2) -induced repression of replication in HDFs. Therefore, the findings presented here suggest that C. asiatica extracts might regulate SIPS by preventing repression of DNA replication and mitosis-related gene expression.
The objective of this work has been the microencapsulation of Asiatic Pennywort (AP) extract with lecithin from soybean. The effect of various quantities of non-ionic surfactant (Montanov82) on liposomes upon physicochemical characteristics as well as their in vitro bio-activities was investigated. An addition of surfactant resulted in a decrease in particle size and an increase in percentage AP entrapment efficiency of liposomes. The surfactant-loaded liposomes demonstrated higher stability than surfactant-free liposomes where higher percentage AP remaining of liposomes can be achieved depending on surfactant concentration. No significant difference was found on AP release profiles among varied surfactant concentrations, although a presence of surfactant resulted in prolonged AP release rate. Liposomal AP with 20% w/w surfactant or higher demonstrated low cytotoxicity, a stronger anti-oxidation effect and collagen production on dermal fibroblast cells when compared with free AP and surfactant-free liposomes, possibly due to better cell internalization and less AP degradation in cells.
PSAPP mice expressing the 'Swedish' amyloid precursor protein and the M146L presenilin 1 mutations are a well-characterized model for spontaneous amyloid beta plaque formation. Centella asiatica has a long history of use in India as a memory enhancing drug in Ayurvedic literature. The study investigated whether Centella asiatica extract (CaE) can alter the amyloid pathology in PSAPP mice by administering CaE (2.5 or 5.0 g/kg/day) starting at 2 months of age prior to the onset of detectable amyloid deposition and continued for either 2 months or 8 months. A significant decrease in amyloid beta 1-40 and 1-42 was detectable by ELISA following an 8 month treatment with 2.5 mg/kg of CaE. A reduction in Congo Red stained fibrillar amyloid plaques was detected with the 5.0 mg/kg CaE dose and long-term treatment regimen. It was also confirmed that CaE functions as an antioxidant in vitro, scavenging free radicals, reducing lipid peroxidation and protecting against DNA damage. The data indicate that CaE can impact the amyloid cascade altering amyloid beta pathology in the brains of PSAPP mice and modulating components of the oxidative stress response that has been implicated in the neurodegenerative changes that occur with Alzheimer's disease.
In this a review concerning TTFCA, its effects on metabolism in the connective tissue of the vascular wall and on the microcirculation are presented and discussed. This compound is effective in venous insufficiency, reducing ankle edema, foot swelling, capillary filtration rate and by improving microcirculatory parameters (RF, VAR PO2-PCO2). TTFCA displays a significant activity in venous hypertensive microangiopathy and its effects are dose-dependent.
The variation of capillary filtration rate (CFR), ankle circumference (AC), and ankle edema (AE) was evaluated in three groups of patients with venous hypertension (ambulatory venous pressure > 42 mmHg) and in a group of normal subjects before and after treatment for four weeks with Total Triterpenic fraction of Centella Asiatica (TTFCA), a venoactive drug acting on the microcirculation and on capillary permeability. Group A (20 patients) was treated with TTFCA 60 mg tid; Group B (20 patients) was treated with 30 mg tid; Group C (12 patients) was treated with placebo; and Group D (10 normal subjects) was treated with TTFCA 60 mg tid in an open study.
Capillary filtration rate was assessed by venous occlusion plethysmography, ankle edema by a new system called AECT (Ankle edema coin tester). Subjective symptoms of venous hypertension were assessed by an analogue scale line considering four symptoms: swelling sensation, restless lower extremity, pain and cramps, and tiredness. CFR, AC, and AE were significantly higher in patients in comparison with normal subjects.
After four weeks of TTFCA treatment there was a significant decrease of the abnormally increased CFR, AC, and AECT time in patients.
This was also greater in the higher dose group. No significant change was observed in the placebo group and in normal subjects treated with TTFCA. Symptoms were also significantly improved in the two groups treated with the active drug according to the dose. No significant changes were observed in the placebo group.
In conclusion the improvement of symptoms by TTFCA observed in patients with venous hypertension was well correlated with the improvement of CFR and ankle edema, and dose ranging showed that 180 mg/day is more effective in improving both symptoms and CFR.
The VSC (vacuum suction chamber) device, a new system to evaluate local capillary permeability, was used with laser Doppler flowmetry to study varia tions of permeability and of the microcirculation in 10 normal subjects; in 22 patients with moderate, superficial venous hypertension; and in 12 patients with postphlebitic limbs and severe venous hypertension. All these patients had distal (ankle and foot edema) in the evening.
After a first assessment these subjects were studied again after two weeks without treatment and after two weeks' treatment with total triterpenic fraction of centella asiatica (TTFCA), tablets, 60 mg, tid.
The VSC produces a wheal on the skin of the perimalleolar region that dis appears (in average) in less than sixty minutes in normal subjects. The disap pearance time (DT) is greater in conditions of increased capillary filtration and permeability.
The three groups of subjects (normal and those with superficial and severe venous hypertension) had significantly different, increasing disappearance time of the wheals at the first observation.
There were no significant changes after two weeks' observation, but after 2 weeks' treatment with TTFCA, there was a significant decrease of DT both in limbs with superficial and with deep venous incompetence.
The improvement (decrease) of the abnormally increased capillary permea bility was associated with a significant improvement of the microcirculation and symptoms (studied by an analogue scale line).
In conclusion this study showed a combined improvement of the microcircu lation and capillary permeability after treatment with TTFCA and the possibil ity of using the VSC to evaluate the effects of drugs (or other treatment) on local capillary permeability in patients with venous hypertension.
In 87 patients with chronic venous hypertensive microangiopathy the efficacy of oral FTTCA (Centella asiatica) administered for 60 days was tested. The microcirculatory effects of two dosages (30 mg bid and 60 mg bid) versus placebo was assessed in a double blind study. The compound was well tolerated and no unwanted effects were observed. Microcirculatory parameters--peri-malleolar skin flux at rest (RF) and transcutaneous PO2 and PCO2--improved as did the abnormally increased RF, PCO2 decreased and PO2 increased in comparison with values measured at inclusion. These results confirm the efficacy of FTTCA in venous hypertensive microangiopathy. Furthermore the effects of FTTCA appear to be dose-related.
Total triterpenic fraction of Centella asiatica (TTFCA) is effective in improving venous wall alterations in chronic venous hypertension and in protecting the venous endothelium. TTFCA is active on connective tissue modulation, improves the synthesis of collagen and other tissue proteins by modulating the action of fibroblasts in the vein wall, and stimulates collagen remodeling in and around the venous wall. This is due to the modulating action of TTFCA on fibroblasts as shown by experiments on the growth of human embryonal fibroblasts. TTFCA has a moderate in-vitro and in-vivo stimulating effect on collagen synthesis and, at higher dosages, an inhibition on the synthesis of collagen and acid mucopolysaccharides. Studies have indicated the role of TTFCA on the synthesis of specific venous wall elements by cell cultures of human embryonal fibroblasts. The tissue-stimulating action is shown by the increased collagen production independent from the stimulation of cell proliferation (this differentiates the action of TTFCA from cell growth factors). TTFCA is active on the microcirculation in venous and diabetic microangiopathy. Signs and symptoms of venous hypertension and edema are improved by treatment. The remodeling on collagen synthesis could be one of the possible mechanisms of actions of TTFCA in the remodeling of echolucent (soft; therefore, with risk of thrombosis and embolization) plaques at the carotid and femoral bifurcation. This compound is safe and well tolerated. In conclusion, several actions of TTFCA in vascular diseases makes the use of this compound very interesting in venous and arterial problems.
The variation of capillary filtration rate (CFR), ankle circumference (AC), and ankle edema (AE) was evaluated in three groups of patients with venous hypertension (ambulatory venous pressure >42 mm Hg) and in a group of normal subjects before and after treatment for 4 weeks with total triterpenic fraction of Centella asiatica (TTFCA), a venoactive drug acting on the microcirculation and on capillary permeability. Group A (20 patients)was treated with TTFCA 60 mg thrice daily, group B (20 patients) was treated with 30 mg thrice daily; group C (12 patients) was treated with placebo; and group D (10 normal subjects) was treated with TTFCA 60 mg thrice daily in a randomized study. Capillary filtration rate was assessed by venous occlusion plethysmography, ankle edema by a new system called AET (ankle edema tester). Subjective symptoms of venous hypertension were assessed by an analogue scale line considering four symptoms: swelling sensation, restless lower extremity, pain and cramps, and tiredness. CFR, AC, and AE were significantly higher in patients in comparison with normal subjects. After 4 weeks of TTFCA treatment, there was a significant decrease of CFR, AC, and AET time in patients. This was also greater in the higher dose group. No significant change was observed in the placebo group and in normal subjects treated with TTFCA. Symptoms were also significantly improved in the two groups treated with the active drug according to the dose. No significant changes were observed in the placebo group. In conclusion, the improvement of signs and symptoms by TTFCA observed in patients with venous hypertension was well correlated with the improvement of CFR and ankle edema. Dose ranging showed that 180 mg/day is more effective in improving symptoms and CFR.
The aim of this prospective, randomized study was to demonstrate whether an oral preparation of TTFCA was effective in improving the microcirculation and edema (leg volume) in venous microangiopathy. Forty patients with venous hypertension were included. Treatment was prescribed for 6 weeks (tablets, 60 mg twice daily). Patients were randomized into a treatment and a placebo group. There were 20 patients in each group. In the treatment group the mean age was 42 (SD 7; M:F = 10:10); in the placebo group, the mean age was 40 (SD 9; M:F = 10:10). Tolerability and compliance were very good; there were no dropouts. At inclusion there were no differences between placebo and treatment group. After treatment there was a decrease in resting flux (29%) and an improvement (increase) in venoarteriolar response (52%); PO2 was increased (7.2%) and PCO2 decreased (9.6%). There was an important decrease in leg volume (66 mL decrease; 1.3% volume variation). The difference in flux, O2-CO2 and volume parameters were significant and clinically important at 6 weeks in the treatment group. In conclusion, TTFCA improves microcirculation and leg volume in venous hypertension. The effects of TTFCA are observed even in a limited sample of patients.
The aim of this study was the evaluation of microcirculatory alterations associated with edema in passengers travelling for more than 3 hours and the study of the effects of TTFCA (total triterpenic fraction of Centella asiatica) on the development of microcirculation alterations and edema, in a prospective, randomized study. Laser Doppler flowmetry (LDF), transcutaneous PO2 and PCO2, rate of ankle swelling (RAS) were used. Subjects were randomized after informed consent into two groups: one control group (no drug or other treatment), and a treatment group (TTFCA 60 mg thrice daily for 2 days before the flight, the day of the flight, and for another day after the flight). Inclusion criteria were age range between 30 and 50, mild-moderate superficial venous disease with varicose veins. Subjects traveled in economy class. In controls there was a progressive increase in CO2, RAS, and edema score and a progressive decrease in flux (RF) and venoarteriolar response with flying time. The variations in all parameters were milder (p>0.05) in the TTFCA group. RAS and edema were significantly lower in the TTFCA-treated group (p<0.025). The progressive increase in RAS, PCO2, and the decrease in VAR and O2 were linearly associated with flight time (up to 10 hours). These results are very interesting and indicate an option for patients prone to edema and microcirculation disturbances during long flights.
The aim of this study was to demonstrate whether total triterpenic fraction of Centella asiatica (TTFCA), was effective in improving the microcirculation in venous hypertension and microangiopathy. Forty patients with severe venous hypertension, ankle swelling, lipodermatosclerosis were included. After informed consent, patients were randomized into a treatment and a placebo group: those in the treatment group received TTFCA (tablets, 60 mg, twice daily for 8 weeks). The two groups of subjects were comparable for age and sex distribution. The mean age was 48 years (SD 9; M:F= 11:11) in the treatment group (22 patients) and 47.6 (SD 7; M:F= 10:8) in the placebo group (18 patients). There were no differences between placebo and treatment group at inclusion; there was no change between inclusion and measurements at 8 weeks in the placebo group. A decrease (p < 0.05) in RF (flux at rest) and RAS (rate of ankle swelling) were observed in the treatment group. The decrease in capillary filtration was associated with improvement in signs and symptoms (p < 0.05). The difference in flux, signs and symptoms, and filtration was clinically important at 8 weeks. No side effects were observed. In conclusion venous microangiopathy was improved by TTFCA treatment.
1. Centella asiatica, an Indian medicinal plant, has been described as possessing central nervous system activity, such as improving intelligence. In addition, we have demonstrated that C. asiatica has cognitive-enhancing and anti-oxidant properties in normal rats. Oxidative stress or an impaired endogenous anti-oxidant mechanism is an important factor that has been implicated in Alzheimer's disease (AD) and cognitive deficits seen in the elderly.
2. Intracerebroventricular (i.c.v.) streptozotocin (STZ) in rats has been likened to sporadic AD in humans and the cognitive impairment is associated with free radical generation in this model. Therefore, in the present study, the effect of an aqueous extract of C. asiatica (100, 200 and 300 mg/kg for 21 days) was evaluated in i.c.v. STZ-induced cognitive impairment and oxidative stress in rats.
3. Male Wistar rats were injected with STZ (3 mg/kg, i.c.v.) bilaterally on the days 1 and 3. Cognitive behaviour was assessed using passive avoidance and elevated plus-maze paradigms on the days 13, 14 and 21. Rats were killed on the day 21 for estimation of oxidative stress parameters (malondialdehyde (MDA), glutathione, superoxide dismutase and catalase) in the whole brain upon completion of the behavioural task.
4. Rats treated with C. asiatica showed a dose-dependent increase in cognitive behaviour in both paradigms. A significant decrease in MDA and an increase in glutathione and catalase levels were observed only in rats treated with 200 and 300 mg/kg C. asiatica.
5. The present findings indicate that an aqueous extract of C. asiatica is effective in preventing the cognitive deficits, as well as the oxidative stress, caused by i.c.v. STZ in rats.
S3A was a RG-I pectin isolated from Centella asiatica that contained Rha, Ara, Gal, Glc and GalA in molar ratio of 1.0:0.6:1.5:0.2:1.1 and had been found to have a backbone composed mainly of the disaccharide repeat unit, -->4)-alpha-D-GalpA-(1-->2)-alpha-L-Rhap-(1-->. Based on methylation analysis, NaIO4 oxidation, partial acid hydrolysis and lithium-treatment, the structural features were elucidated. Side chains of S3A were predominantly linked to O-4 of 1,2,4-linked alpha-L-Rhap. The side chains are comprised of arabinosyl chains, galactosyl chains, arabinogalactosyl chains and short glucosyl chains. A total of 45% Rhap in the backbone was substituted by side chains. The arabinosyl residues were mostly distributed in the arabinosyl side chains. According to the immunological results of S3A and its degraded derivatives, S3A had no immunological activity, but its derivatives had immuno-stimulating activities to some extent.
An attempt has been made to assess the immunomodulatory activity of methanol extracts of whole plant of E. alba (1.6% wedelolactone) and C. asiatica (0.18% of asiaticoside) at five dose levels (dose-response relationship) ranging from 100 to 500 mg/kg body wt. using carbon clearance, antibody titer and cyclophosphamide immunosuppression parameters. In the case of E. alba, the phagocytic index and antibody titer increased significantly and the F ratios of the phagocytic index and WBC count were also significant. Regression analysis showed linearity in patterns of the dose-response relationship, greatest in the case of the phagocytic index, moderate in the WBC count and lowest in the antibody titer. For C. asiatica, significant increases in the phagocytic index and total WBC count were observed and the F ratio of the phagocytic index was also significant. Regressed values revealed maximum linearity in the case of the phagocytic index, moderate linearity in the total WBC count and lowest linearity in the antibody response.
In view of its versatile medicinal properties, the requirement of C. asiatica in pharmaceutical industries has been sharply increasing, thus leading to the over exploitation of this herb. It has already been listed as threatened species by the International Union for Conservation of Nature and National Resources (IUCN) and an endangered species. Therefore application of tissue culture approaches for rapid multiplication of elite clones and germplasm conservation is of vital importance. In recent years, C. asiatica regeneration has been achieved by using leaf derived callus, stem segments and nodal segments as explants, shoot tip and suspension cultures, providing a prerequisite for the generation of bioactive secondary products from this species. However, further studies are still needed to be done for the evaluation of the genetic resources of the plant for variation in morphological, growth, and herb and yield related characters to identify high herb and madecassol yielding populations suitable for use in agronomical and plant breeding programs. A great progress has been made over the past decades in study of biologically active components and bioactivities of C. asiatica, but the results are still unsatisfactory. Even though this highly precious herb is surrounded with multifarious claims, the underlying mechanisms involved in its physiological effects are lacking. More scientific data are required before recommendation for increase in its utilization can be given with confidence.
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