[000i] The present kventton k general relates to the adaptogenic activit of bosweliic acids- polysaccharide compositions wherein the polysaccharide component is not less than. 70% by weight of the said composition, derived from- Besw llia mrrata i combination with- (i) the concentrate -of the liquid endosperm of Cocas wtcif&ra standardized to contain not less than 70% w/w of total dissolved solids or (ii) die extract of Embiica officinalis fhiit standardized to- contain 10% w/w and above of f-Q~galfcyl-p-D-gtucose (β-g!ixcogal!m) and not more than 5% w/w of gallic acid,

BACKGROUND OE THE INVENTION

Description of prior art 00§2 Composition comprising bosweliic acids and polysaccharides obtained from Bosweilia swrai and effects therein in. terms of down-»regulating -pro-kflammatoiy cytokines has been disclosed by Muhammed Majeed etal in United States Patent Application 201.1021 S ! 72» Similar water-soluble bioactive fraction obtained from the gum resin exudate of Boswe Ii rr l -enriched, in polysacchari des having applications in anti-inflammatory and. and -arthritic management methods have also been disclosed k United. States Patent Application 20050192251. The present invention discloses adaptogenic activity of bosweliic acids- poiysaccharide compositions derived from. Bo elUa serrata in combination with (i) the ^■ concentrate of the liquid endosperm- of Corn mmfera standardized to contain not less than 70% W/w of total dissol ve solids or ( i) fee extract ofgrnblica officinalis fruit standardized to contain 10% w/w and above of l-O-gaOoy p-D-gkicose (β-glncogallin) and not more ^' than 5% w w of gallic acid.

While no specific definition of adaptogeiis exist, the term adaptogens or adaptogenic substances are stated to have the capacit to normalize body functions and strengthen systems compromised by stress. The are reported to have a protective effect on health against a wide variety of environmental assaults and emotional conditions. The role of adaptogens k phytotherapy is best siminr rized as follows. Most modem active substances are directed, to well-defined clinical conditions. If preventive actions- are intended, the are specific to a certain disease factor, e.g. vaccines, use of anti-virals* or they are directed to a certain pathological factor with a view to reducing the risk of disease, e.g. cholesterol lowering substances, in contrast to these approaches, the acti on of adaptogens is reported to be neither directed to eliminate the symptoms of already existing diseases nor is the action specific. If used in an already developed disease, adaptogens are thought to create unspecific effects and in this case they mostly are thought to prevent complications of a disease and to strengthen the general state of the organism. Adaptogens are described to promote non-specific resistance of the body against diseases and different types of stress. This is why a pinch broader ^' spectrum of ac tion is attributed to adaptogens as compared to most conventional active substances. Nevertheless, the concept of adaptogens is sufficient to be considered in the assessment of traditional herbal medicinal- products (REFLECTiOM PAPER ON ADAPTOGENIC CONCEPT COMMITTEE ON HERBAL MEDICINAL PRODUCTS

(HMPC), European Medicines Agency, Evaluation of Medicines for Human Use, London, 8 May 2008, Doc, Rei EMEA/HMPC/I02655 2007). For example, the adaptogenic effect of ethanolie extract, of Bacope: monakri in acute stress mice models has been disclosed in Anju, "Baeopa monmeri - Preliminary Study Evaluating its Anti-Stress Activity i Swiss Albino Mice", Research Journal of Pharmaceiiticai, Biological and Chemical Sciences, Volume 2 Issue 4, October - December -2011 , pages 786-794, jOO03|The importance of Nutrition and supplementation strategies focusing on adaptogenic effects- (acute and chronic) like favorable body composition, physical perfomiatiee, metabolism, endurance, recovery from stress and injury and the maintenance of body homeostasis form the crux, of sports nutrition have also been reported in prior art (Dair Australia, ''SPQIITS NUTRITION". Good Health and Nutrition, ABN 60 105 227 987 Level 5, IBM Tower, 60 City Road, Soutlibank Victoria 3006 Australia),

[0004] it is tbus the principle objective of the present invention to disclose adaptogenie activity o boswe!!ic acids -polysaccharide compositions derived from Bosw ttia serrate in combination with it) the concentrate of the liquid endosperm of Cocas mtclfem standardized to contain not less than 70% w/w of total dissolved solids or (ii) the extract of Emhlka officinalis fruit standardized to contain 10% w/w and above of 1 -O-galloyl-p-D-glucose (β-glueogaliin) and not more than 5¾ w/w of gallic acid. Tile inventio describes the tests for adaptogenic properties of said compositions.

(00051 The present invention fulfills the aforesaid objectives and provides farther related advan Cages,

SPMMARY OF THE INVENTION

| O06| Th present invention discloses the adaptogenic activity of bosweJ ^' iic acids- polysaccharide conmositions derived from B weUi serraia in combination with (i) the concentrate of the liquid endosperm of Cocos nucij ra siandardked to contain not less than.70% w of total dissolved solids or (n) the extract of ^' Emhiica .officinalis fruit standardized to contain 10% w/w and above of 1 3-gai.toy!-p-D~giocose (β-g!ucogailin) and not more than 5% w/w of gallic acid,

[Pam 0O07f Other features and advantages of the present invention will become apparent from the- following more detailed description, taken in conjunction with the accompanying images, which illustrate, by way of example, the principle of the invention,

BRIEF DESCRIPTION ^1' OF THE DRAWINGS

00091 ^' .Fig,. I is a graphical representation of the % enhancement in swimming endurance activity of test animals- treated wit 100, 200 and 400 mg/kg body weight per orally of concentrate of liquid endosperm of Cocas mm/em standardized to contain not less than 70% w/w of total dissolved solids (CN) or the extract, f E bliea officinalis fruit standardized to contain. .10% w/ and above of l-O-galloyl-p-D-giuoose φ-gkicoga!lin) and not more than 5% w/w of gallic acid (BO) as- measu ed in comparison to N rma Control animals, jFara 001.0} Fig.2 is a. graphical, representation of % .enhancement in swimming endurance activity of test animals treated with 1.00 mg kg body weight per orally of combined ingredients comprising bos elHc acids-poly saccharide (BP) compositions ^' wherei the polysaccharide component is not less than 70% by weight of the said composition, derived from BosweUia serraia- in combination with the concentrate of the liquid, endosperm of Cocos nmifera Standardized to contain not less than 70% w/w of total dissolved solids as compared with, test animals treated with individual ingredients BP {200 mg kg body weight) and CN 000 mg kg body weight).

[Para .0011] Fig.3 is a graphical representation of % enhancement hi swimming endurance activity of test animals treated with 50 mg/kg body weight hosweiiic acids-polysaccharide compositions wherein the polysaccharide component is not less than 70% by weight of the said composition, derived from Ba&wei ia s rmiit m combination, with the extract of Emblica officinalis fruit standardized to contain 0% w/w and above of !-0-gailoyl«p~D-gh.tcose φ~ glucogailin) and not more than 5% w/w of gallic add as compared witivtest animate treated with individual ^{' '} ingredients BP (200 mg/kg body weight) and EO (50 mg kg body weight). fPara 0012| Fig, 4 is graphical representatio of % increase in hypoxia induction time agains control, of test animals treated, with 50 mg kg body weight per orally of hosweiiic ac-ids- polysaccharide compositions wherein the polysaccharide component is not less than 70% by weight of the said composition, derived- from- Bosweiiiit sermta in combination with the extract of Emblica officinalis fruit standardized to contain 10% w/w and above of 1-O-galloyl-p-D- glueose ( -giticogaliin) and not more than 5% w/w of gallic acid or 100 mg/kg body weight per Orally of bosweliie acids-poly saecn lde com ositions wherein the polysaccharide component is not less tha 70% by weight of the said composition, derived from Ba nttla s&rr ia in combination with the concentrate of the liquid endosperm of Cocas- nuciera standardized to contain not less than 70% w/w of total dissolved solids as compared with tes animals treated with said ingredients alone during recovery against hypoxia,

[Pare 0013 J Fig. 5a sh ows the ex pression of increase in C D3 - T c ell expression in experimental mice subjected to chronic restraint stress, said mice treated with

(1) 50 mg/kg body weight, per orally of boswellic ^' acids-polysaccharide compositions wherein the polysaccharide component is not less than 70% by weigh t of the said composition,, deri ved, .from. Bosw Hki sermta in. combination with the extract of Emblica officinalis fruit standardized to contain. 10% w/w and above of J -Q~galloyI-P~P-glucose (p~gitKogailin) and not more than. 5% w/w of gallic acid;

(2) 100 mg/kg body weight per orally of hosweiiic acids-polysaccharide compositions wherein the polysaccharide component is not less than 70% by weight of the said composition, derived from BosweHia serrata in combination with the concentrate of the Kqiiid endosperm of€acm nwrtfera sta ard zed, to contain not less than. 70% w/ of total, dissolved solids); the effect of compositions (1) and (2) herein above as compared with test, mice treated with said ingredients alone.

Fig. 5b is graphical representation of die effects represented in Fig, 5a.

[Fare 001.4] Fig. 6a sh ws the cytokine IL-2 expression in experimental mice subjected to chronic restraint stress, said mice treated with

(1) 50 mg kg body weight per orally of boswel!ie acids-polysaccharide compositions wherein the polysaccharide component is not less than 70% by weight of the said composition, deri ved from BosweHia serrata i combination with the extract of hli a Officinalis frait standardized to contain 10% w/w and above of i-O-gal!oyl-P-O-glucose ( i-glncogaliin) and not more tha 5% .w/w of gallic acid (i). the concentrate of the liquid endosperm of bcm nuctfem standardized to contain not less than 70% w/ w of total dissol ved solids

(2) 100 mg kg body weight per orally of boswelHc acids-polysaccharide compositions wherein the polysaccharide component is not less than 70% by weight of the said composition, derived from Bo.swellia serrata in combination with the concentrate of the liquid endosperm of Cocos tmcifera standardized to contain not less than 70% w/ of total dissol ed solids; the effect of compositions (1.) and (2) herein above as compared with test mice treated with said ingredients alone.

Fig. 6b is a graphical representation of the effects represented in Fig. 6a,

DESCRIPTION OF THE PREFERRED EMBODIMENTS F£gs,l-6) ^' [Para 0015} in the most preferred embodiment, the present invention .relates to a method of increasing the physiological endurance of mammals in the event of physical stress, said method comprising step of orally administering effective amounts of compositions (adapiogenic compositions) dependin oft the body weight of said mammal, wherein said compositions inelade, a) Bosweilic acids-polysaccharide (BP) composition derived from Bmweiiia serrai wherein the polysaccharide component is not less than 70% by weight of the said composition, combined with ^' the concentrate o die liquid endosperm of Cocos nucifera st d&rdxz&d to contain not less than ^' 70% w/w of total dissolved solids;

h). Bosweilic acids-polysaccharide compositions derived from Bmweiiia serraia wherein the p lysacc aride- component is not less t n 70% by weight of the said composition, combined with- the extract efJimMica officiitatis .fruit standardized to corttfiin 10% w/w •and above of 1 ~OgaOoyi-|3-D~glucose (β-glueogallin) and not more than 5% w/w of gallic cid.

fPara 0016] In another most preferred embodiment,, the- present invention relates to a method of protecting against hypoxic injury in mammals ditriiig physical stress, said method comprising step of orall administering effective amounts of compositions {adaptogenic compositions) depending on the body weight of said mammal, wherein said compositions include,

a) Bosweilic aeids-polysaceharide (BP) compositions- derived from Bmweiiia serraia wherein the polysaccharide component is not less than 70% by weight of the said composition combined with the concentrate of the liquid endosperm of Cocos tmcif ra standardized to contain not less than 70% w/w of total dissolved solids;

b) Bosweilic acids-polysaccharide compositions derived from Bmweiiia serrata wherein the polysaccharide component is not less than 70% by weight of the said composition combined with the extract of Embliea officinalis fruit standardized to contain 10% w/w and above of l-O- ailoyl- -O-glucose (β-glucogaliin) and not more than 5% w/w of gallic acid,

to bring about the effect of increased hypox ia inductio time. [Para 0017f In yet another most preferred 'embo iment, tlie present invention relates to method of increasing CD3+ T cell subsets (population) in mammals under oing physical stress and. stress induced su pression of cellular immunity, said -method -comprising, step of orally inistering effective amounts of compositions (adaptogenie compositions) depending on the body weigh of said mammal, wherein said compositions include,

a) Boswellic aclds-polysaecharide (BP) compositions derived from. Bosw ilia sermia wherein the polysaccharide component is not less than 70% by -weight of the said compositio combined with the concentrate - of the liquid endosperm of Cocas tin fira standardized to contain not less than 70% w/w of total dissol ved solids;

b) Boswellic ackls-polysaceharide compositions derived from B w llia er ta wherein the polysaccharide component is not less than 70% by weight of the said composition combined with the extract, of EmMie officinalis fruit standardized to contain 10% w/w and above of more than 5% w/w of

gallic acid.

[Para 0018] in yet another most preferred embod men , the present invention relates to a method of increasing systemic nterleitkin-2 (1L-2) expression in mammals undergoing physical stress and stress induced suppression of cellular immunity, said method comprising step of orally administering effective amounts of compositions (adapiogentc compositions) depending on th body weight of said ^' .mammal, wherein said compositions include,

a) Boswellic acids-polysaccharide (BP) compositions derived ftom Bosweilia serr f wherein the polysaccharid component is not less than 70% by weight of tlie said -composition combined with the concentrate of the liquid endosperm of Cocos tivcifer siandardized to contain not less than 70% w of total dissolved solids; b) Boswellic acids -polysaccharide composiiioiis derived from Bmwelim serrate wherein the polysaccharide component is not less than 70 by weight of the said composition combined: with the extract of EmMica officinalis -fruit standardized to contain 10% w/w and above of I-O-galloyl-p-D-glueose (β-glucogalli») and not more than 5% w/w of gallic acid.

{Pa a 0019 in yet another most preferred mbodime t, the present invention relates to a method of sustaining neiuoirmscuia coordination m mammals undergoing physical stress, said method comprising step of orally administering effective amounts of compositions (adaptogenie compositions) depending on the body weight of said mammal, wherein said compositions inelnde,

(a) Boswellic acids-poiysa.cehari.de (BP:) compositions derived from Boswel!ici: sermia wherein the polysaccharide component is not less than 70 by weight of the said composition combined with the concentrate of the liquid endosperm of Cams mtcifera -standardized to contain not less than 70% w/w of total dissolved, solids

(©) Boswellic acids-poiysaccharide compositions derived from Bom Ua s&raia wherein the polysaccharide component is not less than 70% b weight of the said composition combined with the extract of Embtt i officinalis fruit standardized to contain 10% w/w and above of l-Q- gailoyl-fi-D-glucos (P~gliicoga!Iin) and. not more than 5% w/w of gallic acid,

{Para 0020] in ye another most -preferred embodiment, the present invention also relates to a method of treating stress induced: h raosnppressive effects in mammalian spleen, thymus and adrenal glands leading to undesirable atrophy or hypertrophy, said method comprising step of ^• orally administering effective amou ts of compositions (adaptogenic compositions) depending on the body weight of said mammal, wherein said compositions include, (a) Bosweliic aclds-polysaceharide (BP) compositions derived, from Bosw&ttkt s&fata wherein the polysaccharide component is not less than 70% by weight of the said composition combined with the concentrate of the liquid endosperm of Cacm tmciftrd standardized to -contain riot less than 70% w/w of total dissolved solids;

(b) Bosweliic acids-polysaccharide compositions derived from Bm ttia sermt ^' wherein the polysaccharide com on nt is not less than 70% by weight of the said coiripositioft combined wi th, the extract of Embiic officinalis fhnt st ndardis d to contain 10% w w and above of l -O- galloyl-P-D-gliiCose (p-glucogallin) and not more than 5% w/w of gallic acid to bring about the effect of attenuating said stress induced atrophy of spleen and thymus glands and hypertrophy of adrenal glands.

[Para 0021] The aforesaid most preferred embodiments are elucidated herein below as illustrative examples.

[Para 0O22J The acute oral safety stud was carried out following OECD -guidelines ^' No, 423. A single dose of the test niaierial(s) BP, BO and CN was administere to a group of three females each u to a dose level of 2000 g kg. The animals were observed tor any gross behavioural changes, for a total of 14 days. No change in general behaviour or arty mortality was observed in groups of animals treated by different doses of the test material for 14 days. For the pharmacological studies, the Applicants tested graded doses ranging from SOmg/kg- to SOOn 'kg of the individual, extracts BP, CN and EO to calculate the most effective dose for the individual extracts in the Swimming endurance test (procedure discussed herein below) [Fig.11 _* The effective doses include BP: 20C¾ng kg. EO; 40 nig/kg and CN: lOOrng kg. Combination of BP (200) CN (100) was then tested at 50, 100 and 200 mg kg for swimming endsrance and the most effective dose of the combination was achieved at lOOtng/kg, S imilarly, Combination of BP (200) EO (400) was then tested at 50, 100 and 200 rag/kg for swimming endurance aid the most effective dos of the combination was achieved at 50mg/'kg. The testing procedures are farther described in detail in EXAMPLE 1 presented herein below. {Para 0023} EXAMPLE i~ SWIMMING ENDURANCE (endurance to physical stress) TEST (Fsgs.l, 2 and 3)

{Para 902 } Amma!s: Male Swiss albino mice

[Para 9025} etgb 25-30 g

{Para 0026} Number of animal s per group ; 06

{Para 0027} Test groups are represented in the folio wing table

[Para 0028} Test materials BP, CN and EO formulated, as adaptogenic compositions mentioned herein above (Groiip Πί and Group I V) were administered per orally to Swiss albino mice (25-30g) of either sex once a day for 14 days. On day 15, one hour after drug administration, the swimmin tune of each animal was measured individually by die Swimming Endurance Test. The animals were allowed to swim inside a perplex glass beaker (30 cm high with 20 cm diameter, containing wate op to 25 cm height) maintained at 26 ± i ¾. The mice were allowed to swim till they got exhausted which was considered as the endpohit. The mea swimming time for each group was caiciiiaied (Fig„2 for group III and Fig. 3 for group TV), Both . (BP÷CK)~Adaptogenie composition; 100 mg kg body weight per oral administration (Group HI) and (BP + EO)- daptogenic composition: 50 rag kg body weight per oral administration (Group IV) were very effective in increasing the endurance capacity of test animals ¼ the Swimming Endurance test.

[Para 0029} EXAMPLE II A-Anti-iMgiie effect [Para 0030] Animals: Swiss albino mice of either sex [Para 0031] Weight; 25-30 [Para 0032] No, of animals per group: 10

[Para 0034] Test material was administered orally once a day for 14 days ^' to animal groups III and I V, On day 15, one -hoar after drag administratio in groups III and !V, the animals were allowed to -swim inside a perplex glass beaker {30 cm high with 20 cm diameter, containing water up to 25 cm height) maintained at 26 ± I ^e C. The mice were allowed, to swim till the got exhausted which: was considered as the endpoin . Group I animals were not exposed to the swimming stress test. Group II animals were exposed to ^' the swimming endurance- test as mentioned, above without being administered test mater als _* Only pre- trained test mice which stayed on a rotating rod at 20 rpm, for more than 5 minutes in three successive ttials for 5 consecutive days, were used in this study. On day 15, the animals of Group .11, i and IV that underwent swimming stiess were immediatel taken out, dried with tissue paper and placed on. the rotating rod. to .monitor anti-fatigue and motor coordination effects. The number of mice that stayed on the rota-rod for 180 seconds or

per oral adtninistratio I fPara 0035] EXAMPLE 2B- Measurement of H poxia time (Fig, 4)

[Para 0036] 3 groups of test animals (Swiss albino mice of either sex; Weight: 25-30 g and number of animals per group: 10) where Grotrp ί includes animals without any test material treatment. Group ΪΙ animals administered (BPH-CN)-Adaptogenie composition: 100 mg'kg body weight per oral -administration for 15 days and Group HI animals administered (BP + BO}- Adaptogenie composition; 50 nig kg body weight pe oral administration animals for 15 days were tested for their ability for resist hypoxia induction. On day 15, one hour after treatment, the hypoxia time was recorded individually or each nimal by placing the animal, in an empty glass jar of 300-n l capacity attached to an electronic watch. The jars were made air-tight with greased glass stoppers and the time until onset of convulsion was recorded as the end point. The results of the hypoxia induction time testin are represented in Fig. 4. The graphs indicate that percentage hypoxia induction time was enhanced for Group 11 (32%) and Group- III (20%) as compared to control untreated Group 1,

[Para 0ft37 EXAMPLE 3-Ciironk restraint stress test jpPara 0038J Male Swiss albino mice, 10-12 weeks old and weighing about 20-22- grams were employed for this study. Mice were .restrained in these 50ml conical polypropylene tubes for 1.2 h during the dark cycle (2000-0800 fa) for 14 days. Experimental animals were divided into groups of eight animals each . Group- 1 served restraint stress control group without treatment "with test material. Group-- ίΐ included animals treated with (BP + EO)-Adaptogeiiic composition: 50 rag/kg body weight per oral administration for 15 days ^' -and subjected to the _: chronic restraint stress test as described before. Group 111 included animals treated (B ^' P+CN)-Adaptogenk composition; 100 mg kg bod weight per oral administration. Following the chronic restraint stress procedure, lymphocyte immuaotyping to evaluate suppression of cellular kmnumty due to stress was done. Blood was taken front the retro-orbital plexus of animals fro all the groups for the assessment of various immune cells surface markers. Murine atnS-CD3+ monoclonal antibodies were used in a miilti parametric- flowc- tometric assay to quantify the lymphocyte subsets associated with the ceii-Mediaied immune response. These tlourochrome labeled monoclonal antibodies were added directly to 1 0 ul. of whole blood, which was then iysed using whole blood lysing reagen (BD Biosciences). Following the final centrifugation, samples were resuspended in phosphate buffer saline (pH _t 7.4) and analyzed directly on the flowcytometer (BD Biosciences) using Cell Quest Pro Software (BD Biosciences) (Fig, 5a). Fig. 5a shows 20.09% CD3 T lymphocyte subsets in the restrained stress control group. Group 11 and ill treated groups show 31.15% and 35.29% CD3+ T lymphocyte subsets indicating recovery of cellular immunity. Further, intracellular Cytokine IL-2 levels were estimated in blood by fkrwcytometr using Phyeoerythrin (PE) labeled lL-2 monoclonal antibodies. Acquisition and the analysis were done directly on Howcytonieter using Cell Quest Pro software (BD Biosciences). Chronic restrained stress condition suppressed the expression of IL-2 to 3.49% in Group 1~ restraint stress control group. The % IL-2 expression increased in Groups II and III to 10.45% and 8.12%.

[Para 0039] EXAMPLE IV- BODY AND ORGAN WEIGHTS fPara 0040] After the last stress session, the body weights of ah the a»ix» ls from all the groups were taken following which the animals were sacrificed and their fh mns, adrenal glands,, and spleen, were removed and weighed. Table B indicates tli¾t (B - G.}s )hA.d¾)togemc composition: 100 nig/kg body weight per oral administration and (BP+EO)- Adapt geaic composition.: 50 rng/kg body weight per oral administration attenuated stress induced atroph of spleen and thymus glands and hypertrophy of adrenal glands.

(Tani )

[Para 11041 J While the invention has been described with reference to a preferred embodiment, it is to be clearly understood by those skilled in the art that -the invention is not liraiied thereto. Rattier, the scope of the invention is to be interpreted only in conjunction with, the appended cla ms*