RIVEW in many parts of India viz; Tamil

 

 

 

 

RIVEW
ARTICLE

 

ANTIARTHRITIC
ACTIVITY OF ANTHRAQUINONES

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FOUND
IN ALOE VERA

 

Key
Words:

Ayurveda, anthraquinones, anthrones,
anhydroglucosyl, aloeemodin,
saponins, mucilaginous,
salicylic acids, parenchymal,
NSAIDS, Prostaglandins, tannins, monosulfonic acid, gibberlin anthranilic, quinidine,
, Barbaloin, aloeemodin-9-anthrone, lsobarbaloin,

INTRODUCTION

Aloe Vera plant belonging to the Asphodelaceae family. The name, aloe, is derived from the Arabic
“alloeh” or Hebrew “halal” meaning bitter shiny substance.
It has a vast traditional role in indigenous system of medicine like Ayurveda, Siddha,
Unani and Homoeopathy (Baby J et al, 2010). Aloe barbadensis miller or Aloe Vera, a semi tropical plant
is one of the 250 species of Aloe. Most commonly used for its medicinal
properties, Aloe Vera or the Sanskrit name “Ghee Kunwar” is a member
of the Lilly family. The plant has lance shaped, sharp pointed, and jagged
& edged leaves. Aloe Vera is found as the wild herb along the coast of South
India. It is under cultivation in fairly large areas in many parts of India
viz; Tamil Nadu, Gujarat, Maharashtra etc. (Das
N et al, 2004). It
is a stemless or very short-stemmed plant growing to 80-100 cm tall, spreading
by offsets and root sprouts. The leaves are thick and fleshy due to water
storage. Leaves are green to gray-green, with a serrated margin. The flowers
are produced on a spike up to 90 cm tall, each flower pendulous, with a yellow
tubular corolla 2-3 cm long (Kumar KPS et al, 2010).  Aloes are often thought to only grow in hot and dry climates,
but they actually grow in a variety of climates including desert, grassland,
and coastal or even alpine locations (Davis UC, 2009). There are more than 200 compounds
found in Aloe barbadensis, about 75 of which have biological activity.

 Aloe Vera leaves
contain a diverse array of compounds, including anthraquinones, anthrones and
their glycosides, aloeemodin enthrone, carbohydrates, proteins, glycoproteins,
amino acids, organic acids, lipids, sugars, vitamins and minerals (Roy
Upton et al, 2012). Aloe Vera contains 75
potentially active constituents: vitamins, enzymes, minerals, sugars, lignin,
saponins, salicylic acids, and amino acids
(Br J Phytotherapy, 1998) Aloe
Vera has a number of uses and mainly they are used as a food preservative and
medicine. Commercially, aloe can be found in pills, sprays, ointments, lotions,
liquids, drinks, jellies, and creams
(Hosseini N et
al, 2012). Various studies have revealed that
Aloe Vera leaf possesses many pharmaceutical activities, including antimicrobial (Bashir
A et al, 2011), anticancer (Naveena
et al, 2011), antioxidant (Miladi
S, et al., 2008)
antidiabetic (Jones K, 2007), antiulcer    (Borra SK, et al,
2011), hepatoprotective
(Chandan
BK et al, 2007) immunomodulatory   (Atul NC et al, 2011)
and many more activities.

Many of the health benefits associated with Aloe Vera have
been attributed to the polysaccharides contained in the gel of the leaves.
(Josias HH, 2008). The Aloe Vera leaf consists of 2 different
parts: central mucilaginous part and peripheral bundle sheath cells. The
parenchymal tissue makes up the inner portion of the aloe leaves and produces a
clear, thin, tasteless jellylike material called an Aloe Vera gel. (Wynn RL et al, 2005). Aloe Vera also
a wound healer for bruises, x-ray burns.
(Shelton RM.1919) insect bites; and anti-helminthic, somatic,
anti-arthritic. (Choi SW et al, 2001).

Recent epidemiological
study shows that about 1% people all over the world are now affected with
rheumatoid arthritis and which exerts a significant impact on the quality of
life (Gracie JA et al, 1999). In all populations,
it is more prevalent among women rather than men. Generally, RA is developed
(almost in 80% cases) from the mid of the fourth decade in life to the last of the
fifth (Albani S et al, 1997).
Medications and lifestyle changes are considered as a treatment for RA.
Conventional treatment provides nonsteroidal antiinflammatory drugs (NSAIDs)
and steroids (typically cortisone injection) (Kavanaugh A et al, 1996). Though these drugs ease the
pain, they are incapable to repair damaged tissues. Although a broad range of
drugs is prescribed for managing the pain and slowing the progression of RA, no
drug is known to cure the disease completely. Moreover stomach ulcer is an
adverse effect observed in RA patients regularly partaking NSAIDS (Okoli CO et al, 2003). These
undesirable side effects frequently force the patients to look for
complementary and alternative medicine (CAM) (Soeken KL et al, 2003). A recent survey indicates that
people suffering from chronic pain in RA and those dissatisfied with allopathic
treatment are more prone to seek alternative medicine, where 60-90% arthritis
patients use CAM (Rao, J et al, 1999). Therefore, it is highly desirable to find out a potential
alternative to eradicate the drawbacks of present allopathic treatment. Natural
products from plants have played a remarkable role to cure and avert different
diseases from ancient times (Kong JM et al, 2003). A study conducted by the World Health Organization (WHO)
has reported that about 80% of the world’s population rely on traditional
medicine. In the USA, nearly 121 drugs are prescribed today, where 90 of them
come from the natural sources, particularly from plants in a direct or indirect
manner (Grindlay D et al, 1986). As a corollary, herbal remedies can be accepted to satisfy
patients having RA it is scientifically palpable that Aloe barbadensis have a
pivotal role to lessen the unbearable pain and inflammation associated with RA (Benowitz S, 1996).

 

 

Some
Reported Constituents of Aloe barbadensis

Groups

Examples

Anthraquinones

Aloin, barbaloin, isobarbaloin,
anthranol, aloetic acid, ester of cinnamic acid, aloe-emodin, aloesin,
emodin, chrysophanic acid, resistanol, anthrone-6-glycosides.

Polysaccharides

Cellulose, glucose,
mannose-6-phosphate, glucose-6-phosphate, aldopento, L-rhamnose

Minerals

Zinc, selenium, calcium, manganese,
copper, chromium, iron, potassium, phosphorus, sodium.

Amino acid

Essential amino acids: Isoleucine,
leucine, lysine, methionine, phenylalanine, threonine, Valine and tryptophan.
Nonessential amino acids: alanine, arginine, asparagine, cysteine, glutamic
acid, glycine, histidine, proline, serine, tyrosine, glutamine, and aspartic
acid.

Vitamins

A, B1, B2, B3, B5, B6, and B12, C, and
E

Enzymes

Amylase, bradykinase, catalase,
carboxypeptidase, cellulase, lipase, oxidase, alkaline phosphatase,
proteolytiase, creatine, phosphokinase

Sterols

Cholesterol, campesterol, luperol, and
– sitosterol

Miscellaneous

Prostaglandins,
tannins, magnesium lactate, resins, mansions, and proteins such as lectins,
monosulfonic acid, and gibberlin.

(Abdullah-Al-Nahain
et al, 2014)

The key symptom of rheumatoid arthritis is painful
inflammation of the joints. There have been some scientific studies about Aloe Vera
and its use for easing arthritis pain. Oral Aloe Vera could be used in the
treatment of chronic non-cancer pain, particularly that caused by
osteoarthritis (Cowan D, 2010) Aloe Vera
administration topically also inhibits inflammation (Davis RH et al, 1989) The gel of the Aloe Vera plant
can also be applied directly to the swollen and painful joints. The gel will
provide relief of joint immobility and pain, due to its anti-inflammatory
properties. Recently, it has been demonstrated that aloe gel acts as an
effective gel base to prepare nimesulide Emulgel with a significant
anti-inflammatory effect for topical delivery in rheumatoid arthritis and other
inflammatory conditions (Vandana KR et al, 2014).

Rheumatoid arthritis (RA), which is a form of an auto-immune bone
destructive disease, affects at least 1% of the population in the
industrialized world with higher frequency in women. In severe cases of
rheumatoid arthritis, the synovial inflammation leads to particular cartilage
damage, bone erosion, and subsequent change in joint integrity. Usually,
peripheral joints are involved (Abdel-Nasser
A et al, 2008)

Rheumatoid arthritis is a painful and crippling systemic
disease for which there is no cure. The best experimental model for studying
rheumatoid arthritis in humans is the adjuvant-induced arthritis in rats. One
of the group of compounds found in Aloe is the anthraquinones. These substances
have been recognized for their use in veterinary medicine against
inflammation.Evaluate the anti inflammatory and antiarthritic activity of
anthraquinone, anthracene, cinnamicacid, and anthranilic acid found in the Aloe
vera plant, and show what contribution each ingredient makes toward the total
activity found in Aloe.Aloe gel extract has anti-inflammatory and
antiarthriticactivity.Combinations of Aloe with ascorbic acid, thymus extract,
and RNA significantly improved the activity. The chemical makeup of Aloe holds
a valuable key to antiarthritic activity that could be used by podiatrists to
treat patients. No doubt anthraquinones have a bearing on the healing and
pain-killing effectiveness of the fresh leaf gel. Few people understand the
meaning of the anthraquinone complex in Aloe. Many studies verify the successful
treatment of burns, ulcers, and dermatitis, but no one knows why Aloe has these
healing qualities.The propose to test the antiarthritic and anti-inflammatory
activity of anthraquinone, anthracene, cinnamic acid, and anthranilic acid in
an adjuvant arthritis model in order to determine if there are possible
ingredients that can be used to treat rheumatoid arthritis. This approach will
help us understand the antiarthritic activity of Aloe. The purpose of this
study is to determine, in part, the active elements in Aloe so as to unlock the
mystery of the gel. Many medicines in common use today, such as digitalis and
quinidine, were derived in a similar way from barks and leaves.

Adult male Sprague-Dawley rats (175 to 200 cm, 12/group)
were injected with heat-killed Mycobacterium butyricum.
Two experiments were conducted
together. One study investigated the effect of anthraquinones on the prevention
of adjuvant arthritis. Anthraquinone had the most preventive antiarthritic activity
recorded of the three Aloe compounds tested. Anthraquinone inhibited
inflammation 67.3%, which was the largest response next to anthranilic acid.
Anthracene had no antiarthritic activity, but a 17.6% inhibition of
inflammation was obtained in  the
inflammatory paws. This is about one third the effect seen with anthraquinone
and anthranilic acid. A good positive anti-inflammatory response was also
obtained with cinnamic acid (32.0%) (Robert H at el, 1986).

Aloe Vera has been used for medicinal purposes by humankind
for centuries, including for the treatment of burns, as an anti-viral, for
inhibition of tumor cells and, not least, for treatment of arthritis despite
this, generally, the evidence for the effectiveness of Aloe Vera is anecdotal
or from relatively small studies. However, this evidence warrants further
investigation. Furthermore, the findings of pre-clinical and animal studies
also support the suggestion that Aloe Vera is an efficacious anti-inflammatory
agent (Yoo et al, 2008). Studies
have found that ingestion of Aloe Vera on a daily basis can help prevent and
cause a regression of arthritis. Aloe gel also reduces pain related to tendonitis
and injuries. When applied directly to the area of pain, Aloe Vera penetrates
the skin to soothe the pain. Biological Vehicle Acts as a biological vehicle to
aid penetration and absorption of other bio- active ingredients into deep
tissue (Surjushe A et al, 2008). In
a small uncontrolled study of 12 rheumatoid arthritis  patients (age range 24-84, male, 70%),
clinically diagnosed by x-ray as having evidence of duodenal lesions were
treated with oral Aloe Vera gel emulsion. Within a year, repeat x-ray
examination indicated evidence of complete healing in 11 patients. (Blitz et al, 1963).

Anthraquinones
the bitter reddish yellow exudates, located beneath the outer green rind,
contains anthraquinones and their derivatives, Barbaloin,
aloeemodin-9-anthrone, lsobarbaloin, Anthrone-C-glycosides and creaminess.
These are phenolic compounds, traditionally known as laxatives. These compounds
exert a powerful purgative effect, when in large amount, but when smaller they
appear to aid absorption from the gut and are potent antimicrobial agents and
possess powerful analgesic effects. (Joseph
B et al, 2010)

 

One
of the major groups of compounds of Aloe barbadensis is anthraquinones, which
have been strongly identified as potent inhibitors of inflammation (Yagi A et al, 2002). Chemical
structures of some anthraquinones having a beneficial effect in RA treatment
are presented (Figure 1). It has been claimed that emotion from Aloe
barbadensis can play a major beneficial role in RA. The mechanism through which
emotion can play a beneficial role in arthritis. The authors reported that emotion
can inhibit the nuclear translocation and DNA binding of NF-B subunits, which
are correlated with its inhibitory effect on cytoplasmic IB degradation. In
addition, they showed that emodin inhibited the osteoclast differentiation
induced by momocyte- colony stimulating factor (M-CSF) and receptor activation
of NF-B ligand in bone marrow macrophages (Hwang
JK et al, 2013).

 

Anthraquinones found in Aloe may be
responsible for the healing properties and anti-inflammatory activity recorded.
This study has shown both anti-inflammatory and antiarthritic activity that can
be improved by combining Aloe with ascorbic acid, thymus extract, and RNA.
Since the chemical composition of Aloe holds a valuable key to its activity,
the antiarthritic and anti-inflammatory activity of the anthraquinone complex
in the adjuvant arthritis rat was tested. Anthraquinone and cinnamic acid
exhibited anti-inflammatory activity in the prevention study. Anthranilic acid
prevented inflammation as well as arthritis. Both anthraquinone and cinnamic
acid exhibited activity in the regression phase. This work proves that the
anthraquinone complex contributes to the healing properties of Aloe. (Robert
H et al,
1986).

 

Rheumatoid
arthritis is a debilitating disease affecting millions of people throughout the
world and is more present in elderly people. The disease affects mobility and
as such the affected population has to suffer both physically with possible
concomitant mental depression. Available allopathic drugs cannot cure the
disease and relieves only the symptoms and also are not without adverse
effects, and so there is a need for newer drugs to treat this disease. Plants
have always proved to be a rich source of drugs. Phytochemicals present in Aloe
barbadensis can provide relief to RA patients through promoting wound healing,
as well as reducing inflammation and relieving pain, which are common symptoms
of affected patients. From that viewpoint, Aloe barbadensis and its
phytochemical constituents has the potential for further studies leading to
newer and more efficacious drugs against rheumatoid arthritis.

(Abdullah-Al-Nahain
et al, 2014)

 

 

 

 

 

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