|Year : 2016 | Volume
| Issue : 5 | Page : 29-33
Safety and efficacy of health supplement (Pegaga based product)
Firdaus Abd Rahman1, Chua Say Tiong2, Kah Seng Lee3, Amir Heberd Abdullah2, Long Chiau Ming4
1 Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Selangor, Malaysia
2 Department of Environmental Health, Faculty of Health Sciences, Universiti Teknologi MARA, Bertam, Penang; Vector-borne Diseases Research Group (VERDI), Pharmaceutical and Life Sciences CoRe, Universiti Teknologi MARA, Shah Alam, Selangor, Malaysia
3 School of Pharmacy, Curtin University, Perth, Australia
4 Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam; Vector-borne Diseases Research Group (VERDI), Pharmaceutical and Life Sciences CoRe, Universiti Teknologi MARA, Shah Alam, Selangor, Malaysia
|Date of Web Publication||26-May-2016|
Firdaus Abd Rahman
Level 11, FF1 Building, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam, Bandar Puncak Alam, Selangor 42300
Source of Support: None, Conflict of Interest: None
Purpose: The aim of this review is to evaluate the safety and efficacy of a product containing Pegaga and to understand the related marketing issues.
Methodology: A review regarding registration of product was conducted by examining the registration in National Pharmaceutical Control Bureau (NPCB), Ministry of Health (MOH) of Malaysia and the profile of product was evaluated by assessing the online MIMS, Micromedex, and www.globinmed.com. Besides that, an electronic search was conducted through searching at ScienceDirect, EMBASE, CINAHL to assess the safety and efficacy of the product. Malaysia Advertisement Board was referred to evaluate the marketing issue using Dimaz Kapsul Herbanika Pegaga Plus as a case example.
Results: According to (NPCB), (MOH), Dimaz Kapsul Herbanika Pegaga Plus is listed under traditional product with registration number “MAL13095058T.” They claimed this product contained herbs called Centella asiatica and have many indications as their advertisement. Dimaz Kapsul Herbanika Pegaga Plus widely advertised throughout social media such as Facebook, website services, and online marketing. Thus, there are a few issues related to marketing that against the Medicine Advertisement Board. Moreover, a review on safety and efficacy of C. asiatica from study on human reported that C. asiatica is effective in enhanced working memory, for improvement of the signs and symptoms of chronic venous insufficiency, reducing the sensory symptoms in diabetic mellitus neuropathy, and improves physical performance in elderly. Study on animal and in vitro reported C. asiatica have an anti-tumor effect, anti-nociceptive effects, wrong healing property, antigenotoxic effect, and reduce blood glucose by demonstrate glucose-fiber binding.
Conclusions: Most traditional products claim contained herbs and have many indication although not proven by evidence based. Hence, consumers must be more selective before buying any health products. MOH continuing demonstrate enforcement action and educating the public in this matter. More research also must be conducted to confirm the efficacy and the appropriate dose for a particular situation either for prevention or treatment of disease.
Keywords: Centella asiatica, efficacy, Pegaga, safety, traditional product
|How to cite this article:|
Abd Rahman F, Tiong CS, Lee KS, Abdullah AH, Ming LC. Safety and efficacy of health supplement (Pegaga based product). Arch Pharma Pract 2016;7, Suppl S1:29-33
|How to cite this URL:|
Abd Rahman F, Tiong CS, Lee KS, Abdullah AH, Ming LC. Safety and efficacy of health supplement (Pegaga based product). Arch Pharma Pract [serial online] 2016 [cited 2019 Jun 20];7, Suppl S1:29-33. Available from: http://www.archivepp.com/text.asp?2016/7/5/29/183034
| Pharmacokinetics|| |
Pharmacokinetics parameter of active ingredients
Centella asiatica selected triterpenes (CAST) is a standardized mixture of the most significant active ingredients of C. asiatica leaves, namely the glycoside asiaticoside (AS) (36–44%) and the genins asiatic and madecassic acid (56–64%), assayed by high-performance liquid chromatography (HPLC).
Standardized extracts of C. asiatica leaves and AS have been reported to be well tolerated in experimental animals, especially by oral route. The pharmacokinetics of CAST has been investigated in healthy volunteers. After oral administration in single doses (30–60 mg) or after a 7-day treatment (30 or 60 mg twice daily), following a randomized cross-over design. Plasma concentrations of asiatic acid were measured using HPLC assay method. AS is reported to contribute to the plasma levels of asiatic acid because of its in vivo conversion into asiatic acid. After repeated administrations of CAST peak plasma concentrations (Cmax), 24 h area under curve and half-life (t½) values were significantly higher than those obtained after the corresponding single doses.
In toxicological studies AS did not show any sign of toxicity up to the dose of 1 g/kg after oral administration, whereas the toxic dose by intramuscular application to mice and rabbits was 40–50 mg/kg. In teratological studies in rabbits, a standardized extract of C. asiatica leaves did not show any teratogenic effect.
| Marketing Strategy and Compliance to Laws|| |
There are several approaches used by distributor of this product in advertisements and marketing. They manage a website and Facebook page. Through these methods, they not only advertise Dimaz Kapsul Herbanika Pegaga Plus product, but it included all their other variety products. Through further online searching, there are several other blogs and Facebook accounts that advertise this product.
Besides information about their company and products, customer can communicate with dealers via personal messenger (in Facebook) or short message service or WhatsApp with number given by them. Through further discussions in this way, users can get more information about products such as leaflets and testimony compilation.
According to Medicines (Advertisement and Sale) Act (MASA) 1956, “Advertisement” mean “includes any notice, circular, report, commentary, pamphlet, label, wrapper or other document, and any announcement made orally or by any means of producing or transmitting light or sound.” With this definition, the way and materials used in the advertising of this product must also comply with the MASA 1956. Violation of Section 3(1)(a) - Prevention or treatment of the disease and conditions of human as specified in the schedule 1 (refer to schedule 1 in MASA 1956).
Some indications that advertising by distributor of this product mislead consumers. To avoid action may be taken by the pharmacy enforcement, they use different words for the technically.
This is a few examples of words used by distributor to avoid enforcement action taken to them.
Violation of Section 3(1)(c) improves the condition or functioning of the human kidney or heart, or improving the sexual function or sexual performance of human beings. There is a word used by distributor in the advertisement and violate Section 3(1)(c) such as “relieve kidney problems” because it is regarding improving the condition or functioning of the human kidney. This is not allowed.
Violation to Section 4B: Advertisement of medicines to be approved. According to this section, “No person shall take any part in the publication of any advertisement referring to any article, or articles of any description, in terms which are calculated to lead to the use of that article of that description as a medicine, an appliance or a remedy for the purpose of treatment or prevention of diseases or conditions of human beings other than the diseases and conditions specified in Subsection 3(1), unless such advertisement has been approved by the Medicine Advertisements Board.”
Section 5: Provisions as to offences Section 3, 4, and 4B under MASA 1956. If the advertiser (distributor in this case) in the case of first conviction, he/she can be fined not exceeding 3000 ringgit or to imprisonment for any term not exceeding 1 year or to both.
| Methodology|| |
An electronic search of ScienceDirect, EMBASE, CINAHL and database of abstracts of reviews of effects for studies, trial, and reviews using the following research criteria were carried out:
All the studies submitted were reviewed. The following websites were searched for reviews and reports for additional information: (MIMS, Micromedex, www.globinmed.com).
| Efficacy and Safety|| |
Research/study on human
From systematic searching, only four study C. asiatica on human found as follow:
- A randomized, placebo-controlled, double-blind study investigated the effect of C. asiatica on cognitive function of the healthy elderly volunteer. Twenty-eight healthy elderly participants received the plant extract at various doses ranging 250, 500 and 750 mg once daily for 2 months. Results showed that the high dose of the plant extract enhanced working memory. Improvements of self-rated mood were also found following the C. asiatica treatment 
- A systematic review to assess the efficacy of C. asiatica for improvement of the signs and symptoms of chronic venous insufficiency (CVI) from 13 electronic databases including the Cochrane Central Register of Controlled Trials for randomized controlled trials. Eight studies met the inclusion criteria. Results show that C. asiatica may be beneficial for improving signs and symptoms of CVI 
- A randomized, double-blind, placebo-controlled study was conducted to examine the effect of CAST in diabetic mellitus neuropathy on 33 subjects within 52-week on. This study show CAST is safe and well tolerated at a dose of 240 mg QD and effective in reducing the sensory symptoms subjectively and preventing the reduction of the sensory nerve action potential amplitude objectively 
- A double-blind, placebo-controlled, randomized study effect of C. asiatica to improves physical performance and health-related quality of life in healthy elderly. Eighty healthy elderly were randomly assigned to receive placebo or standardized extract of C. asiatica at doses of 250, 500, and 750 mg once daily for 90 days. The results showed that after 2 months of treatment, C. asiatica at doses of 500 and 750 mg/day increased lower extremity strength assessed via the 30-s chair stand test. In addition, the higher doses of C. asiatica could improve the life satisfaction subscale within the physical function subscale.
Research/study on animal and in vitro
Another study about C. asiatica found is a study on animal and in vitro study as follow: A study on rat performed to examines the anti-tumor effect of the crude extract (CE) of C. asiatica as well as its partially purified fractions (AF) from chromatographic procedures by both in vitro short and long-term chemosensitivity and in vivo tumor model test systems. AF dose dependently inhibited the proliferation of the transformed cell lines significantly more than did the CE and other solvent fractions. Fifty percent effective doses on 3 h exposure to AF were 17 and 22 mg/ml for Ehrlich ascites tumor cells and Dalton's lymphoma ascites tumor cells, respectively. However, practically no toxic effects were detected in normal human lymphocytes. AF also significantly suppressed the multiplication of mouse lung fibroblast (L-929) cells at a concentration of 8 mg/ml in long-term culture. Oral administration of the extracts (CE and AF) retarded the development of solid and ascites tumors and increased the life span of these tumor bearing mice. Tritiated thymidine, uridine, and leucine incorporation assay suggest that the fraction acts directly on DNA synthesis.
Another animal study conducted to evaluate of prophylactic efficacy and possible mechanisms of AS based standardized extract of C. asiatica (L.) urban leaves (INDCA) in animal models of a migraine. This study show INDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.
A study on rabbit was carried out to evaluate the effects of C. asiatica on the proliferation and migration of rabbit corneal epithelial (RCE) cells in the in vitro wound healing model. RCE cells were cultured with or without supplementation of C. asiatica aqueous extract. Results were found that supplementation of C. asiatica significantly inhibited RCE cells proliferation (P < 0.05) at the concentration of 1000 ppm. The conclusion from this study proves supplementation of C. asiatica aqueous extract at low concentrations could be useful to promote corneal epithelium wound healing.
An in vitro study was conducted to access antigenotoxic effect of C. asiatica induced by cyproterone acetate (CPA) on human lymphocytes using chromosomal aberrations and sister chromatid exchanges as parameters. The treatment of the two doses of CPA, i.e., 20 and 30 µM was given along with the C. asiatica extract at several dosages The results of this study suggest that the plant extract per se do not have genotoxic potential, but can modulate the genotoxicity of CPA on human lymphocytes in vitro.
A study was conducted to explore the possible effects, C. asiatica extract and insoluble fiber on carbohydrate absorption, insulin secretion, insulin sensitivity, and glucose utilization. They measured fasting blood glucose and performed glucose tolerance test, in Type 2 diabetic rats. The result confirmed significant glucose-fiber binding was demonstrated in the in vitro models.
| Potential Risk to General Public|| |
In Malaysia, the use of Traditional and Complementary Medicine (T and CM) is a complement to modern medicine. This means that patients who get the disease must be treated with modern medicine as a main treatment. The use of T and CM such as the use of herbs or supplement health to diseased patients must get advice from doctor or pharmacist.
In the case of this products, many indications shown on the labeling and advertisement of products. It is not necessarily true because it not dependent on scientific research and evidenced-based. Most indications traditional health products relied on testimonies and experiences of previous customers. Therefore, the public should not be misled by the advertisement.
Consumers should also be informed of the need to inform your pharmacist or doctor in case of any adverse effects from the use of the product. Pharmacist or Doctor who receives the report will report to National Pharmaceutical Control Bureau and further analysis can be carried out. This action can help other users from experiencing same adverse effects if the product is harmless to health.
| Recommendations and Conclusions|| |
In most traditional products, we hardly saw any products containing same herbal ingredients have the same indication. This is because they often do not refer to the evidenced-based study, but based on their experiences.
In the context of this product, it is better product label be changed to be more general claim. As examples for body fresh and vitality, specific label indication to treat or prevent any disease or condition is not justified and could mislead consumers.
However, no doubt herb C. asiatica have properties that are available for generations. Therefore, more research must be conducted to confirm the efficacy (indications) and the appropriate dose for a particular situation either for prevention or treatment of disease.
Malaysia has a good health facilities either hospital or health clinic. The facilities offer to all urban and rural residents, especially to Malaysia citizens. However, the things need to be improved is to educate consumers, especially in the recruitment of health products. Know your medicine campaign is one of the campaigns that deal with this challenge and must continue. In addition to the campaign in the organizing of program, distribution of flyers/posters, exhibitions, advertising continuously in hardcopy/print and electronic media must also be carried out continuously. Users should know and use their rights as consumers.
Financial support and sponsorship
This work was supported by Research Acculturation Grant Scheme: RAGS/1/2014/SKK07/UITM//2. The authors would like to express their gratitude to Ministry of Higher Education and Universiti Teknologi MARA (UiTM), Malaysia for financial support for this research.
Conflicts of interest
There are no conflicts of interest.
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