Definition : Aloe Vera Gel is the colourless mucilaginous gel obtained from the

parenchymatous cells in the fresh leaves of Aloe vera (L) Burm. f. (Liliaceae)
Synonyms : Aloe barbadensis Mill., Aloe chinensis Bak., A. elongata Murray, A. indica
Royle, A. officinalis Forsk., A. perfoliata L., A. rubescens DC, A. vera L. var. littoralis
König ex Bak., A. vera L. var. chinensis Berger, A. vulgaris Lam. Most formularies and
reference books regard Aloe barbadensis Mill. as the correct species name, and Aloe vera
(L.) Burm. f. as a synonym. However, according to the International Rules of Botanical
Nomenclature, Aloe vera (L.) Burm. f. is the legitimate name for this species. The genus
Aloe has also been placed taxonomically in a family called Aloeaceae.
Selected vernacular names : Aloe vera gel, aloe gel.
Description : Succulent, almost sessile perennial herb; leaves 30–50 cm long and 10 cm
broad at the base; colour pea-green (when young spotted with white); bright yellow
tubular flowers 25–35 mm in length arranged in a slender loose spike; stamens frequently
project beyond the perianth tube.
Plant material of interest : liquid gel from the fresh leaf. Aloe Vera Gel is not to be
confused with the juice, which is the bitter yellow exudate originating from the bundle
sheath cells of the leaf. The drug Aloe consists of the dried juice.
General appearance : The gel is a viscous, colourless, transparent liquid.
Organoleptic properties : Viscous, colourless, odourless, taste slightly bitter.
Microscopic characteristics : Not applicable.
Geographical distribution : Probably native to north Africa along the upper Nile in the
Sudan, and subsequently introduced and naturalized in the Mediterranean region, most of
the tropics and warmer areas of the world, including Asia, the Bahamas, Central
America, Mexico, the southern United States of America, south-east Asia, and the West
Indies.
General identity tests : To be established in accordance with national requirements.
Purity tests
Microbiology : The test for Salmonella spp. in Aloe Vera Gel should be negative.
Acceptable maximum limits of other microorganisms are as follows.
For external use : aerobic bacteria—not more than 102/ml; fungi—not more than 102/ml;
enterobacteria and certain Gram-negative bacteria—not more than 101/ml;
Staphylococcus spp.—0/ml. (Not used internally.)
Moisture : Contains 98.5% water.
Pesticide residues : To be established in accordance with national requirements. For
guidance, see WHO guidelines on quality control methods for medicinal plants and
guidelines on predicting dietary intake of pesticide residues.
Heavy metals : Recommended lead and cadmium levels are not more than 10 and
0.3mg/kg, respectively, in the final dosage form.
Radioactive residues : For analysis of strontium-90, iodine-131, caesium-134, caesium-
137, and plutonium-239, see WHO guidelines on quality control methods for medicinal
plants.
Other tests : Chemical tests for Aloe Vera Gel and tests for total ash, acid-insoluble ash,
alcohol-soluble residue, foreign organic matter, and water-soluble extracts to be
established in accordance with national requirements.
Aloe Vera Gel
Chemical assays : Carbohydrates (0.3%), water (98.5%) Polysaccharide composition
analysis by gas–liquid chromatography.
Major chemical constituents : Aloe Vera Gel consists primarily of water and
polysaccharides (pectins, hemicelluloses, glucomannan, acemannan, and mannose
derivatives). It also contains amino acids, lipids, sterols (lupeol, campesterol, and
-sitosterol), tannins, and enzymes. Mannose 6-phosphate is a major sugar component.
Dosage forms : The clear mucilaginous gel. At present no commercial preparation has
been proved to be stable. Because many of the active ingredients in the gel appear to
deteriorate on storage, the use of fresh gel is recommended.
Preparation of fresh gel : harvest leaves and wash them with water and a mild chlorine
solution. Remove the outer layers of the leaf including the pericyclic cells, leaving a
“fillet” of gel. Care should be taken not to tear the green rind which can contaminate the
fillet with leaf exudate. The gel may be stabilized by pasteurization at 75–80°C for less
than 3 minutes. Higher temperatures held for longer times may alter the chemical
composition of the gel.
Medicinal uses
Uses supported by clinical data : None.
Uses described in pharmacopoeias and in traditional systems of medicine : Aloe Vera Gel
is widely used for the external treatment of minor wounds and inflammatory skin
disorders. The gel is used in the treatment of minor skin irritations, including burns,
bruises, and abrasions. The gel is further used in the cosmetics industry as a hydrating
ingredient in liquids, creams, sun lotions, shaving creams, lip balms, healing ointments,
and face packs.
Aloe Vera Gel has been traditionally used as a natural remedy for burns. Aloe Vera Gel
has been effectively used in the treatment of first- and second-degree thermal burns and
radiation burns. Both thermal and radiation burns healed faster with less necrosis when
treated with preparations containing Aloe Vera Gel. In most cases the gel must be freshly
prepared because of its sensitivity to enzymatic, oxidative, or microbial degradation. Aloe
Vera Gel is not approved as an internal medication, and internal administration of the gel
has not been shown to exert any consistent therapeutic effect.
Uses described in folk medicine, not supported by experimental or clinical data : The
treatment of acne, haemorrhoids, psoriasis, anemia, glaucoma, petit ulcer, tuberculosis,
blindness, seborrhoeic dermatitis, and fungal infections.
Pharmacology
Wound healing : Clinical investigations suggest that Aloe Vera Gel preparations
accelerate wound healing. In vivo studies have demonstrated that Aloe Vera Gel
promotes wound healing by directly stimulating the activity of macrophages and
fibroblasts. Fibroblast activation by Aloe Vera Gel has been reported to increase both
collagen and proteoglycan synthesis, thereby promoting tissue repair. Some of the active
principles appear to be polysaccharides composed of several monosaccharides,
predominantly mannose. It has been suggested that mannose 6-phosphate, the principal
sugar component of Aloe Vera Gel, may be partly responsible for the wound healing
properties of the gel. Mannose 6-phosphate can bind to the growth factor receptors on the
surface of the fibroblasts and thereby enhance their activity. Furthermore, acemannan, a
complex carbohydrate isolated from Aloe leaves, has been shown to accelerate wound
healing and reduce radiationinduced skin reactions. The mechanism of action of
acemannan appears to be twofold. First, acemannan is a potent macrophage-activating
agent and therefore may stimulate the release of fibrogenic cytokines. Second, growth
factors may directly bind to acemannan, promoting their stability and prolonging their
stimulation of granulation tissue. The therapeutic effects of Aloe Vera Gel also include
prevention of progressive dermal ischaemia caused by burns, frostbite, electrical injury
and intra-arterial drug abuse. In vivo analysis of these injuries demonstrates that Aloe
Vera Gel acts as an inhibitor of thromboxane A2, a mediator of progressive tissue
damage. Several other mechanisms have been proposed to explain the activity of Aloe
Vera Gel, including stimulation of the complement linked to polysaccharides, as well as
the hydrating, insulating, and protective properties of the gel.
Because many of the active ingredients appear to deteriorate on storage, the use of fresh
gel is recommended. Studies of the growth of normal human cells in vitro demonstrated
that cell growth and attachment were promoted by exposure to fresh Aloe vera leaves,
whereas a stabilized Aloe Vera Gel preparation was shown to be cytotoxic to both normal
and tumour cells. The cytotoxic effects of the stabilized gel were thought to be due to the
addition of other substances to the gel during processing.
Anti-inflammatory : The anti-inflammatory activity of Aloe Vera Gel has been revealed
by a number of in vitro and in vivo studies. Fresh Aloe Vera Gel significantly reduced
acute inflammation in rats (carrageenin-induced paw oedema), although no effect on
chronic inflammation was observed. Aloe Vera Gel appears to exert its anti-inflammatory
activity through bradykinase activity and thromboxane B2 and prostaglandin F2
inhibition. Furthermore, three plant sterols in Aloe Vera Gel reduced inflammation by up
to 37% in croton oil-induced oedema in mice. Lupeol, one of the sterol compounds found
in Aloe vera, was the most active and reduced inflammation in a dose dependent manner.
These data suggest that specific plant sterols may also contribute to the anti-inflammatory
activity of Aloe Vera Gel.
Burn treatment : Aloe Vera Gel has been used for the treatment of radiation burns.
Healing of radiation ulcers was observed in two patients treated with Aloe vera cream,
although the fresh gel was more effective than the cream. Complete healing was
observed, after treatment with fresh Aloe Vera Gel, in two patients with radiation burns
(30). Twenty-seven patients with partial thickness burns were treated with Aloe Vera Gel
in a placebo-controlled study. The Aloe Vera Gel-treated lesions healed faster (11.8 days)
than the burns treated with petroleum jelly gauze (18.2 days), a difference that is
statistically significant (t-test, P 0.002).
Contra indications : Aloe Vera Gel is contraindicated in cases of known allergy to
plants in the Liliaceae.
Warnings : No information available.
Precautions : No information available concerning general precautions, or precautions
dealing with carcinogenesis, mutagenesis, impairment of fertility; drug and laboratory
test interactions; drug interactions; nursing mothers; paediatric use; or teratogenic or non-
teratogenic effects on pregnancy. Adverse reactions : There have been a few reports of
contact dermatitis and burning skin sensations following topical applications of Aloe
Vera Gel to dermabraded skin. These reactions appeared to be associated with
anthraquinone contaminants in this preparation. A case of disseminated dermatitis has
been reported following application of Aloe Vera Gel to a patient with stasis dermatitis.
An acute bullous allergic reaction and contact urticaria have also been reported to result
from the use of Aloe Vera Gel.
Posology : Fresh gel or preparations containing 10–70% fresh gel.

Regulation and quality control of herbal drugs in

Korea

, a,
Don Woong Choi , Jong Hwan Kima, So Yean Choa, Dal Hwan Kima and
Seung Yeup Changa

a
Department of Herbal Medicines Evaluation, Korea Food and Drug Administration,
Seoul, 122-704, South Korea

Available online 15 October 2002.

Abstract

Korea has a great diversity in resources of medicinal plants. The traditional herbal
medicines and their preparations have been widely used in Korea as well as in China and
Japan for thousands of years. One of the characteristics of Korean herbal medicine
preparations is that all the herbal medicines are incorporated into an extractor at the same
time and extracted with boiling water during the decoction process. In this process, a
variety of interactions between the active components of several herbal medicines may
occur. This is the main reason why quality control of oriental herbal drug is more difficult
than that of western herbal drug. In this paper, we would like to present an overview of
the characteristics of regulation and quality control of herbal medicines in Korea.

Keywords: Korean herbal medicine; Quality control; Decoction

Article Outline

1. Introduction
2. Present status of herbal medicines in Korea
2.1. Distribution of medicinal plants
2.2. Production of herbal medicines
2.3. Import and export of herbal medicines
2.4. Scientific researches on herbal medicines
2.5. Standard herbal medicines listed in official compendiums
3. Some regulations concerning herbal medicines
4. Quality control of herbal medicines in Korea
5. International harmonization upon specifications of herbal medicines
6. Conclusion
References
The growth of pharmaceutical industry is based on continuing
success in producing new products whether they are used as
therapeutic or prophylactic agents. The role of R&D is pivotal
in this endeavor.

Pharmaceutical research is aimed at meeting the medical needs of the population for whom
appropriate therapeutic remedies are not available or at those that are available are unsafe for
prophylactic use for various disorders. While meeting medical needs, research also has to ensure
that market needs for such exist and that the product will command sales and profits
proportionate to investments. In cases where there are mismatches between these two, the
products suffer the status of orphan drugs. The selection of an appropriate R&D portfolio is a
strategic management exercise for a company, which should take into account apart from
medical needs, innovative potential for success and available resources.

WHO Guidelines for Quality Standardized Herbal Formulations

a.Quality control of crude drugs material, plant preparations and finished products.

b.Stability assessment and shelf life.

c.Safety assessment; documentation of safety based on experience or toxicological studies.

d. Assessment of efficacy by ethnomedical informations and biological activity evaluations.

The bioactive extract should be standardized on the basis of active principles or major
compounds along with the chromatographic fingerprints (TLC, HPTLC, HPLC and GC). The
standardization of crude drug materials include the following steps:

1.Authentication (Stage of collection, parts of the plant collected, regional status, botanical
identity like phytomorphology, microscopical and histological analysis, taxonomical identity, etc.)

2.Foreign matter (herbs collected should be free from soil, insect parts or animal excreta, etc.)
3.Organoleptic evaluation (sensory characters – taste, appearance, odor, feel of the drug, etc.)

4.Tissues of diagnostic importance present in the drug powder.

5. Ash values and extractive values.

6.Volatile matter

7.Moisture content determination

8.Chromatographic and spectroscopic evaluation. TLC, HPTLC, HPLC methods will provide
qualitative and semi quantitative information about the main active constituents present in the
crude drug as chemical markers in the TLC fingerprint evaluation of herbals (FEH). The quality of
the drug can also be assessed on the basis of the chromatographic fingerprint.

9.Determination of heavy metals – e.g. cadmium, lead, arsenic, etc.

10.Pesticide residue – WHO and FAO (Food and Agricultural Organization) set limits of
pesticides, which are usually present in the herbs. These pesticides are mixed with the herbs
during the time of cultivation. Mainly pesticides like DDT, BHC, toxaphene, aldrin cause serious
side-effects in human beings if the crude drugs are mixed with these agents.

11.Microbial contamination – usually medicinal plants containing bacteria and molds are coming
from soil and atmosphere. Analysis of the limits of E. coli and molds clearly throws light towards
the harvesting and production practices. The substance known as afflatoxins will produce serious
side-effects if consumed along with the crude drugs.

Limits for Microbial Contamination

Microorganism Finished product Raw materials

E. coli 101 104
Salmonella - -
Total aerobic bacteria 105 -
Enterobacteria 103 -

Afflatoxins should be completely removed or should not be present.

12.Radioactive contamination – Microbial growth in herbals are usually avoided by irradiation.

This process may sterilize the plant material but the radioactivity hazard should be taken into
account. The radioactivity of the plant samples should be checked accordingly to the guidelines of
International Atomic Energy (IAE) in Vienna and that of WHO.

In order to obtain quality oriented herbal products care should be taken right from the proper
identification of plants; season and area of collection, extraction, isolation and verification
process.

Chemical and instrumental analyses are routinely used for analyzing synthetic drugs to confirm its
authenticity. In the case of herbal drugs, however the scene is different especially for polyherbal
formulation, as there is no chemical or analytical methods available. Therefore biological-
screening methods can be adopted for routine checkup of herbal drugs and formulations. In the
case of herbal drugs, the quality of raw materials and products can be furnished by regular
pharmacognostic identifications and phytochemical analysis. The herbal formulations in general
can be standardized schematically as to formulate the medicament using raw materials collected
from different localities and a comparative chemical efficacy of different batches of formulation
are to be observed. The preparation with better clinical efficacy are to be selected. After all the
routine physical, chemical and pharmacological parameters are to be checked for all the batches
to select the final finished product and to validate the whole manufacturing process.

The stability parameters for the herbal formulations which includes physical parameters, chemical
parameters, and microbiological parameters.

Physical parameters include color, appearance, odor, clarity, viscosity, moisture content, pH,
disintegration time, friability, hardness, flowability, flocculation, sedimentation, settling rate and
ash values.

Chemical parameters includes limit tests, extractive values, chemical assays, etc.

Chromatographic analysis of herbals can be done using TLC, HPLC, HPTLC and GC, UV,
Fluorimetry, GC-MS, etc.

Microbiological parameters include total viable content, total mold count, total enterobacterial and
their count. Limiters can be utilized as a quantitative or semiquantitative tool to ascertain and
control the amount of impurities like the reagents used during abstraction of various herbs,
impurities coming directly from the manufacturing vessels, impurities from the solvents, etc.

Chemical decomposition of substances present in the formulation also produces several toxic or
impure compounds during storage in undesirable conditions. Contaminants may come directly
from the atmosphere also. This include mainly dust, sulfur dioxide, H2S, CO2, Arsenic, moisture,
etc.

The guidelines set by WHO can be summarized as follows:

a.Reference to the identity of the drug. Botanical evaluation – sensory characters, foreign organic
matter, microscopical, histological, histochemical evaluation, quantitative measurements, etc.

b.Reference to the physiochemical character of the drug. Chromatographic profiles, ash values,
extractive values, refractive index, polarimetric readings, moisture content, volatile oil content,
etc.

c.Reference to the pharmacological parameters. Biological activity profiles, bitterness values,

haemolytic index, astringency, swelling factor, foaming index, etc.

d.Toxicity details – heavy metals like cadmium, lead, arsenic, mercury, etc. Pesticide residues.

Maximum residue limits =

Acceptable daily index x body weight x extraction factor

--------------------------------------------------------------- x Therapeutic doses

Mean daily intake of drug x safety factor x 100

e.Microbial contamination – Total viable aerobic count, pathogenic bacteria like enterobacteria, E.
coli, salmonella, Pseudomonous aeruginosa, Staphylococcus aureus, etc. and presence of
afflatoxins etc.
f. Radioactive contamination.

Modern herbal ayurvedic monographs

In the modern herbal ayurvedic monographs the standardization parameters are discussed in a
comprehensive way. According to the modern ayurvedic monograph the quality control protocols
include the following:

Title, synonyms, publications related to that plant, constituents present, analytical methods.

Descriptive evaluation: Description of the drug, phytomorphological, microscopical, organoleptic

evaluations, foreign matter, foreign minerals, etc.

Physicochemical parameters

Identity: Physical and chemical identity, chromatographic finger prints, ash values, extractive
values, moisture content.

Strength: Ethanol and water extractive values, volatile oil and alkaloidal assays, quantitative
estimation protocols, etc.

Biological Activity Evaluation

Bitterness values, astringency, swelling factor, form index, hemolytic index, etc.

Toxicological evaluation

Pesticide residues, heavy metals, microbial contamination like total viable aerobic count,
pathogens like E. coli, Salmonella, P. aeruginosa, S. aureus, Enterobacteria, etc.

Aflatoxins

The presence of aflatoxins can be determined by chromatographic methods using standard

aflatoxins B1, B2, G1, G2 mixtures. Aflatoxin is a product of the microbial strain Aspergillus flavus.

Radioactive Contaminants

Therapeutic Evaluation

Classical Evaluation as per Ayurvedic Literatures

Classical therapeutical attributes like Rasna, Guna, Virya, Vipaka and Karma classical
formulations, doses, storage conditions.

The quality of the raw materials can be tested according to the following format:

Name of the drug (English, Regional names, Exact botanical nomenclature)

Part of the plant used

Area of collection
Distribution details

Season of Crop

Time and year of collection

Pesticide and insecticides

Condition of the drug (fresh or dry)

Form of the drug (powdered or intact or cuttings like etc.)

CONCLUSION

The subject of herbal drug standardization is massively wide and deep. There is so much to know
and so much seemingly contradictory theories on the subject of herbal medicines and its
relationship with human physiology and mental function.

For the purpose of research work on standardization of herbal formulations and neutraceuticals a
profound knowledge of the important herbs found in India and widely used in Ayurvedic
formulation is of utmost importance.

India can emerge as the major country and play the lead role in production of standardized,
therapeutically effective ayurvedic formulation. India needs to explore the medicinally important
plants. This can be achieved only if the herbal products are evaluated and analyzed using
sophisticated modern techniques of standardization such as UV-visible, TLC, HPLC, HPTLC, GC-
MS, spectrofluorimetric and other methods.