RIVEWARTICLE ANTIARTHRITICACTIVITY OF ANTHRAQUINONESFOUNDIN ALOE VERA  KeyWords:Ayurveda, anthraquinones, anthrones,anhydroglucosyl, aloeemodin,saponins, mucilaginous,salicylic acids, parenchymal,NSAIDS, Prostaglandins, tannins, monosulfonic acid, gibberlin anthranilic, quinidine,, Barbaloin, aloeemodin-9-anthrone, lsobarbaloin,INTRODUCTIONAloe 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 plantis one of the 250 species of Aloe.

Most commonly used for its medicinalproperties, Aloe Vera or the Sanskrit name “Ghee Kunwar” is a memberof 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 SouthIndia. It is under cultivation in fairly large areas in many parts of Indiaviz; Tamil Nadu, Gujarat, Maharashtra etc.

(DasN et al, 2004). Itis a stemless or very short-stemmed plant growing to 80-100 cm tall, spreadingby offsets and root sprouts. The leaves are thick and fleshy due to waterstorage. Leaves are green to gray-green, with a serrated margin. The flowersare produced on a spike up to 90 cm tall, each flower pendulous, with a yellowtubular 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 compoundsfound in Aloe barbadensis, about 75 of which have biological activity. Aloe Vera leavescontain a diverse array of compounds, including anthraquinones, anthrones andtheir glycosides, aloeemodin enthrone, carbohydrates, proteins, glycoproteins,amino acids, organic acids, lipids, sugars, vitamins and minerals (RoyUpton et al, 2012). Aloe Vera contains 75potentially active constituents: vitamins, enzymes, minerals, sugars, lignin,saponins, salicylic acids, and amino acids(Br J Phytotherapy, 1998) AloeVera has a number of uses and mainly they are used as a food preservative andmedicine. Commercially, aloe can be found in pills, sprays, ointments, lotions,liquids, drinks, jellies, and creams(Hosseini N etal, 2012). Various studies have revealed thatAloe Vera leaf possesses many pharmaceutical activities, including antimicrobial (BashirA et al, 2011), anticancer (Naveenaet al, 2011), antioxidant (MiladiS, et al., 2008)antidiabetic (Jones K, 2007), antiulcer    (Borra SK, et al,2011), hepatoprotective(ChandanBK et al, 2007) immunomodulatory   (Atul NC et al, 2011)and many more activities. Many of the health benefits associated with Aloe Vera havebeen attributed to the polysaccharides contained in the gel of the leaves.

(Josias HH, 2008). The Aloe Vera leaf consists of 2 differentparts: central mucilaginous part and peripheral bundle sheath cells. Theparenchymal tissue makes up the inner portion of the aloe leaves and produces aclear, thin, tasteless jellylike material called an Aloe Vera gel. (Wynn RL et al, 2005). Aloe Vera alsoa wound healer for bruises, x-ray burns.(Shelton RM.

1919) insect bites; and anti-helminthic, somatic,anti-arthritic. (Choi SW et al, 2001). Recent epidemiologicalstudy shows that about 1% people all over the world are now affected withrheumatoid arthritis and which exerts a significant impact on the quality oflife (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 thefifth (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 thepain, they are incapable to repair damaged tissues. Although a broad range ofdrugs is prescribed for managing the pain and slowing the progression of RA, nodrug is known to cure the disease completely. Moreover stomach ulcer is anadverse effect observed in RA patients regularly partaking NSAIDS (Okoli CO et al, 2003). Theseundesirable side effects frequently force the patients to look forcomplementary and alternative medicine (CAM) (Soeken KL et al, 2003). A recent survey indicates thatpeople suffering from chronic pain in RA and those dissatisfied with allopathictreatment are more prone to seek alternative medicine, where 60-90% arthritispatients use CAM (Rao, J et al, 1999). Therefore, it is highly desirable to find out a potentialalternative to eradicate the drawbacks of present allopathic treatment.

Naturalproducts from plants have played a remarkable role to cure and avert differentdiseases 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 traditionalmedicine. In the USA, nearly 121 drugs are prescribed today, where 90 of themcome from the natural sources, particularly from plants in a direct or indirectmanner (Grindlay D et al, 1986). As a corollary, herbal remedies can be accepted to satisfypatients having RA it is scientifically palpable that Aloe barbadensis have apivotal role to lessen the unbearable pain and inflammation associated with RA (Benowitz S, 1996).   SomeReported 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-Nahainet al, 2014)The key symptom of rheumatoid arthritis is painfulinflammation of the joints. There have been some scientific studies about Aloe Veraand its use for easing arthritis pain.

Oral Aloe Vera could be used in thetreatment of chronic non-cancer pain, particularly that caused byosteoarthritis (Cowan D, 2010) Aloe Veraadministration topically also inhibits inflammation (Davis RH et al, 1989) The gel of the Aloe Vera plantcan also be applied directly to the swollen and painful joints. The gel willprovide relief of joint immobility and pain, due to its anti-inflammatoryproperties. Recently, it has been demonstrated that aloe gel acts as aneffective gel base to prepare nimesulide Emulgel with a significantanti-inflammatory effect for topical delivery in rheumatoid arthritis and otherinflammatory conditions (Vandana KR et al, 2014).Rheumatoid arthritis (RA), which is a form of an auto-immune bonedestructive disease, affects at least 1% of the population in theindustrialized world with higher frequency in women. In severe cases ofrheumatoid arthritis, the synovial inflammation leads to particular cartilagedamage, bone erosion, and subsequent change in joint integrity.

Usually,peripheral joints are involved (Abdel-NasserA et al, 2008)Rheumatoid arthritis is a painful and crippling systemicdisease for which there is no cure. The best experimental model for studyingrheumatoid arthritis in humans is the adjuvant-induced arthritis in rats. Oneof the group of compounds found in Aloe is the anthraquinones. These substanceshave been recognized for their use in veterinary medicine againstinflammation.

Evaluate the anti inflammatory and antiarthritic activity ofanthraquinone, anthracene, cinnamicacid, and anthranilic acid found in the Aloevera plant, and show what contribution each ingredient makes toward the totalactivity found in Aloe.Aloe gel extract has anti-inflammatory andantiarthriticactivity.Combinations of Aloe with ascorbic acid, thymus extract,and RNA significantly improved the activity. The chemical makeup of Aloe holdsa valuable key to antiarthritic activity that could be used by podiatrists totreat patients. No doubt anthraquinones have a bearing on the healing andpain-killing effectiveness of the fresh leaf gel. Few people understand themeaning of the anthraquinone complex in Aloe.

Many studies verify the successfultreatment of burns, ulcers, and dermatitis, but no one knows why Aloe has thesehealing qualities.The propose to test the antiarthritic and anti-inflammatoryactivity of anthraquinone, anthracene, cinnamic acid, and anthranilic acid inan adjuvant arthritis model in order to determine if there are possibleingredients that can be used to treat rheumatoid arthritis. This approach willhelp us understand the antiarthritic activity of Aloe. The purpose of thisstudy is to determine, in part, the active elements in Aloe so as to unlock themystery of the gel. Many medicines in common use today, such as digitalis andquinidine, 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 conductedtogether. One study investigated the effect of anthraquinones on the preventionof adjuvant arthritis. Anthraquinone had the most preventive antiarthritic activityrecorded of the three Aloe compounds tested.

Anthraquinone inhibitedinflammation 67.3%, which was the largest response next to anthranilic acid.Anthracene had no antiarthritic activity, but a 17.6% inhibition ofinflammation was obtained in  theinflammatory paws. This is about one third the effect seen with anthraquinoneand anthranilic acid. A good positive anti-inflammatory response was alsoobtained with cinnamic acid (32.

0%) (Robert H at el, 1986).Aloe Vera has been used for medicinal purposes by humankindfor centuries, including for the treatment of burns, as an anti-viral, forinhibition of tumor cells and, not least, for treatment of arthritis despitethis, generally, the evidence for the effectiveness of Aloe Vera is anecdotalor from relatively small studies. However, this evidence warrants furtherinvestigation. Furthermore, the findings of pre-clinical and animal studiesalso support the suggestion that Aloe Vera is an efficacious anti-inflammatoryagent (Yoo et al, 2008). Studieshave found that ingestion of Aloe Vera on a daily basis can help prevent andcause a regression of arthritis. Aloe gel also reduces pain related to tendonitisand injuries. When applied directly to the area of pain, Aloe Vera penetratesthe skin to soothe the pain.

Biological Vehicle Acts as a biological vehicle toaid penetration and absorption of other bio- active ingredients into deeptissue (Surjushe A et al, 2008). Ina 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 weretreated with oral Aloe Vera gel emulsion. Within a year, repeat x-rayexamination indicated evidence of complete healing in 11 patients. (Blitz et al, 1963).Anthraquinonesthe 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 compoundsexert a powerful purgative effect, when in large amount, but when smaller theyappear to aid absorption from the gut and are potent antimicrobial agents andpossess powerful analgesic effects. (JosephB et al, 2010) Oneof the major groups of compounds of Aloe barbadensis is anthraquinones, whichhave been strongly identified as potent inhibitors of inflammation (Yagi A et al, 2002). Chemicalstructures of some anthraquinones having a beneficial effect in RA treatmentare presented (Figure 1).

It has been claimed that emotion from Aloebarbadensis can play a major beneficial role in RA. The mechanism through whichemotion can play a beneficial role in arthritis. The authors reported that emotioncan inhibit the nuclear translocation and DNA binding of NF-B subunits, whichare correlated with its inhibitory effect on cytoplasmic IB degradation.

Inaddition, they showed that emodin inhibited the osteoclast differentiationinduced by momocyte- colony stimulating factor (M-CSF) and receptor activationof NF-B ligand in bone marrow macrophages (HwangJK et al, 2013). Anthraquinones found in Aloe may beresponsible for the healing properties and anti-inflammatory activity recorded.This study has shown both anti-inflammatory and antiarthritic activity that canbe 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 complexin the adjuvant arthritis rat was tested. Anthraquinone and cinnamic acidexhibited anti-inflammatory activity in the prevention study.

Anthranilic acidprevented inflammation as well as arthritis. Both anthraquinone and cinnamicacid exhibited activity in the regression phase. This work proves that theanthraquinone complex contributes to the healing properties of Aloe. (RobertH et al,1986). Rheumatoidarthritis is a debilitating disease affecting millions of people throughout theworld and is more present in elderly people.

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