EP3979817A1 - Composition for prostaglandin transporter inhibition and related therapeutic applications - Google Patents
Composition for prostaglandin transporter inhibition and related therapeutic applicationsInfo
- Publication number
- EP3979817A1 EP3979817A1 EP19931817.1A EP19931817A EP3979817A1 EP 3979817 A1 EP3979817 A1 EP 3979817A1 EP 19931817 A EP19931817 A EP 19931817A EP 3979817 A1 EP3979817 A1 EP 3979817A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- composition
- extract
- contain
- para
- standardized
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/385—Concentrates of non-alcoholic beverages
- A23L2/39—Dry compositions
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
- A61K36/8962—Allium, e.g. garden onion, leek, garlic or chives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the invention in general relates to composition comprising plant extracts. More specifically the present invention pertains to compositions for inhibiting prostaglandin transporter (PGT) and related therapeutic applications.
- PTT prostaglandin transporter
- PCs Prostaglandins
- PCs are naturally occurring unsaturated fatty acids which are implicated in mediating a variety of pathophysiological processes and homeostatic functions in different organs. They are derived from arachidonic acid by the action of cyclooxygenase isoenzymes.
- PGE2 prostaglandin E2
- PGE2 prostacyclin
- PPD2 prostaglandin D2
- PAF2a prostaglandin F2ct
- the encoded protein is involved in mediating the uptake and clearance of prostaglandins in numerous tissues and organs which include Brain, Colon, Heart, Kidney, Liver, Lung, Ovary, Pancreas, Placenta, Prostate, Skeletal muscle. Small intestine, Spleen and Vascular endothelium.
- PGT is now increasingly becoming a target for the development of drugs to curtail the harmful effects brought about by the uptake of PGs into the cells and related clinical conditions.
- NSAIDs are also known to inhibit the generation and effect of the PGs.
- these synthetic drags have increased side effects and there exists a need for a safe and natural alternative to mitigate the effects of PGs by inhibiting PGT.
- Active molecules derived from plants are now being used extensively for treating many diseases and disorders.
- a plant based composition for inhibiting or blocking PGT is not reported.
- the present invention solves the above problem by disclosing a natural plant based composition for the inhibition of PGT and to bring about related therapeutic effects.
- the present invention provides a natural plant based composition for use as a prostaglandin transporter inhibitor.
- the invention discloses a composition comprising effective doses of Allium sativum extract standardized to contain not less than 0.3% w/w S-allylcysteine, Beta vulgaris extract standardized to contain not less than 2% w/w nitrates, Nigella sativa extract standardized to contain 0.1% - 5% w/w thymoquinone, about 0.01% - 10% w/w thymohydroquinone, about 20% - 95% w/w fatty acids, about 0.001%-3% w/w a-hederin or hederagenin, and Terminalia arjuna extract standardized to contain 3% w/w arjunoglucosides for use a PGT inhibitor
- the invention also discloses a method for the therapeutic management of hypertension in mammals using a composition
- Allium sativum extract standardized to contain not less than 0.3% w/w S-allylcysteine
- Beta vulgaris extract standardized to contain not less than 2% w/w nitrates
- Nigella sativa extract standardized to contain 0.1% - 5% w/w thymoquinone, about 0.01% - 10% w/w thymohydroquinone, about 20% - 95% w/w fatty acids, about 0.001%-3% w/w a-hederin or hederagenin
- Terminalia arjuna extract standardized to contain 3% w/w arjunoglucosides.
- the invention discloses a method for conferring cardio protection in mammals using a composition comprising Allium sativum extract standardized to contain not less than 0.3% w/w S-allylcysteine, Beta vulgaris extract standardized to contain not less than 2% w/w nitrates, Nigella sativa extract standardized to contain 0.1% - 5% w/w thymoquinone, about 0.01% - 10% w/w thymohydroquinone, about 20% - 95% w/w fatty acids, about 0.001%-3% w/w a-hederin or hederagenin, and Terminalia arjuna extract standardized to contain 3% w/w arjunoglucosides.
- Allium sativum extract standardized to contain not less than 0.3% w/w S-allylcysteine
- Beta vulgaris extract standardized to contain not less than 2% w/w nitrates
- Nigella sativa extract
- Fig. 1 is a graphical representation showing the effect of formulation on PGE2 metabolism in MDCK cells, the expression of extracellular PGE2 was analysed in the culture media
- Fig, 2 is a graphical representation showing the effect of formulation on PGE2 metabolism in MDCK cells, the expression of intra cellular PGE2 was analysed in the cell lysate
- Fig, 3 is a graphical representation showing the expression of plasma PGT in rats treated with different concentrations of the formulation
- Fig. 4 is a graphical representation showing the expression of nitric oxide levels in rats treated with different concentrations of the formulation
- Fig. 5A is a graphical representation showing the systolic BP in rats treated with different concentrations of the formulation
- Fig. SB is a graphical representation showing the diastolic BP in rats treated with different concentrations of the formulation
- Fig. 6 is a graphical representation showing the heart rate in rats treated witii different concentrations of the formulation
- Fig. 7 is a graphical representation showing the mean arterial pressure in rats treated with different concentrations of the formulation
- Fig. 8 is a graphical representation showing the AST levels in rats treated witii different concentrations of the formulation
- Fig. 9 is a graphical representation showing the LDH and CK-MB levels in rats treated with different concentrations of the formulation DESCRIPTION OF PREFERRED EMBODIMENTS
- Tlie invention is described in detail with each preferred embodiment for better understanding and to enable a person moderately skilled in the art to manifest or practice the invention.
- the invention discloses a plant based composition comprising of Allium sativum extract, Beta vulgaris extract Nigella sativa extract and Terminalia arjuna extract hi a related aspect, the Allium sativum extract is standardized to contain not less than 0.3% S-allylcysteine. In another related aspect, the Beta mlgaris extract is standardized to contain not less than 2% nitrates.
- the Nigella sativa extract is standardized to contain 0.1% - 5% w/w thymoquinone, about 0.01% - 10% w/w thymohydroquinone, about 20% - 95% w/w fatty acids, about 0.001%-3% w/w a-hederin or hederagenin.
- the Terminalia arjuna extract is standardized to contain 3% w/w arjunoglucosides.
- the composition is used as prostaglandin transporter inhibitor.
- the composition is used for the therapeutic management of hypertension.
- the composition is used as a cardio protective agent.
- composition is formulated with pharmaceutically/nutraceutically acceptable bioavailability enhancers, antioxidants, excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies or eatables.
- the present invention discloses a method for inhibiting prostaglandin transporter in mammalian cells, said method comprising step of bringing into contact mammalian cells expressing prostaglandin transporter with a composition comprising 30-60% w/w Allium sativum extract, 10-30% w/w Beta vulgaris extract, 5-15% w/w Nigella sativa extract and 10-30% w/w Terminalia arjuna extract.
- the Allium sativum extract is standardized to contain not less than 0.3% S-allylcysteine.
- the Beta vulgaris extract is standardized to contain not less than 2% nitrates.
- the Nigella sativa extract is standardized to contain 0.1% - 5% w/w thymoquinone, about 0.01% - 10% w/w thymohydroquinone, about 20% - 95% w/w fatty acids, about 0.001%-3% w/w a-hederin or hederagenin.
- the Terminalia arjuna extract is standardized to contain 3% w/w arjunoglucosides.
- the prostaglandins are selected from the group comprising prostaglandin E2 (PGE2), prostacyclin (PGI2), prostaglandin D2 (PGD2), and prostaglandin F2a (PGF2a).
- PGE2 prostaglandin E2
- PGE2 prostacyclin
- PPD2 prostaglandin D2
- PPF2a prostaglandin F2a
- the mammalian cells are human cells.
- the invention discloses a composition comprising 30-60% w/w Allium sativum extract, 10-30% w/w Beta vulgaris extract, 5-15% w/w Nigella sativa extract and 10-30% w/w Terminalia arjuna extract for use as a prostaglandin transporter inhibitor.
- the Allium sativum extract is standardized to contain not less than 0.3% S-allylcysteine.
- the Beta vulgaris extract is standardized to contain not less than 2% nitrates.
- the Nigella sativa extract is standardized to contain 0.1% - 5% w/w thymoquinone, about 0.01% - 10% w/w thymohydroquinone, about 20% - 95% w/w fatty acids, about 0.001%-3% w/w a-hederin or hederagenin.
- the Terminalia arjuna extract is standardized to contain 3% w/w arjunoglucosides.
- the prostaglandins are selected from the group comprising prostaglandin E2 (PGE2), prostacyclin (PGI2), prostaglandin D2 (PGD2), and prostaglandin F2a (PGF2a).
- the invention discloses a method for the therapeutic management of hypertension in mammals, comprising step of administering an effective dose of a composition comprising 30-60% w/w Allium sativum extract, 10-30% w/w Beta vulgaris extract, 5-15% w/w Nigella sativa extract and 10-30% w/w Terminalia arjuna extract to mammals to bring about a. reduction in symptoms of hypertension.
- the management of hypertension is brought about by inhibiting/blocking prostaglandin transporter.
- tire symptoms of hypertension are selected from the group comprising elevated systolic and diastolic pressure, elevated mean arterial pressure, elevated heart rate and decreased nitric oxide levels.
- the effective dose of the composition is 50 - 400 mg/kg bodyweight.
- the mammal is human.
- the composition is formulated with pharmaceutically/nutraceutically acceptable bioavai lability enhancers, antioxidants, excipients, adjuvants, diluents or carriers and administered in. the form of tablets, capsules, syrups, gummies, powders, suspensions , emulsions, chewables, candies or eatables.
- the invention discloses a composition comprising 30-60% w/w Allium sativum extract, 10-30% w/w Beta vulgaris extract, 5-15% w/w Nigella sativa extract and 10-30% w/w Terminalia arjuna extract method for the therapeutic management of hypertension and related symptoms in mammals.
- the management of hypertension is brought about by inhibiting/blocking prostaglandin transporter.
- the symptoms of hypertension are selected from the group comprising elevated systolic and diastolic pressure, elevated mean arterial pressure, elevated heart rate and decreased nitric oxide levels.
- the effective dose of the composition is 50 - 400 mg/kg bodyweight.
- the mammal is human.
- the composition is formulated with pharmaceutically/nutraceutically acceptable bioavailability enhancers, antioxidants, excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies or eatables.
- the invention discloses a method for the therapeutic management of cardiovascular complications in mammals, comprising step of administering an effective dose of a composition comprising 30-60% w/w Allium sativum extract, 10-30% w/w Beta vulgaris extract, 5-15% w/w Nigella sativa extract and 10-30% w/w Terminalia arjuna extract to mammals to bring about a reduction in symptoms of cardiovascular complications.
- the management of cardiovascular complications is brought about by inhibiting/blocking prostaglandin transporter.
- the symptoms of cardiovascular complications are selected from the group comprising elevated systolic and diastolic pressure, elevated mean arterial pressure, elevated heart rate, and increased levels of cardiac markers.
- the cardiac markers are selected from the group comprising Aspartate aminotransferase, Lactate dehydrogenase and Creatine kinase.
- the effective dose of the composition is 50 - 400 mg/kg bodyweight.
- the mammal is human.
- the composition is formulated with pharmaceutically/nutraceutically acceptable bioavailability enhancers, antioxidants, excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies or eatables.
- the invention discloses a composition comprising 30-60% w/w Allium sativum extract, 10-30% w/w Beta vulgaris extract, 5-15% w/w Nigella sativa extract and 10-30% w/w Terminalia arjuna for the therapeutic management of cardiovascular complications and related symptoms in mammals.
- the management of cardiovascular complications is brought about by inhibiting/blocking prostaglandin transporter.
- the symptoms of cardiovascular complications are selected from the group comprising elevated systolic and. diastolic pressure, elevated mean arterial pressure, elevated heart rate and increased levels of cardiac markers.
- the cardiac markers are selected from the group comprising Aspartate aminotransferase, Lactate dehydrogenase and Creatine kinase.
- the effective dose of the composition is 50 - 400 mg/kg bodyweight.
- the mammal is human.
- the composition is formulated with pharmaceutically/nutraceutically acceptable bioavailability enhancers, antioxidants, excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies or eatables.
- the invention discloses a composition comprising 30-60% w/w Allium sativum extract, 10-30% w/w Beta vulgaris extract, 5-15% w/w Nigella sativa extract and 10-30% w/w Terminalia arjuna extract for the inhibition of PGT.
- the abovementioned extracts are reported to elicit cardioprotective and anti-hypertensive effects individually.
- Some of the medicinal properties of the above extracts are mentioned herein below:
- Allium sativum is a well known plant used in the traditional system of Ayurveda. It is reported to elicit many therapeutic effects against different disorders which include cardiovascular diseases, regulating blood pressure, lowering blood sugar and cholesterol levels. It is also effective against bacterial, viral, fungal and parasitic infections and is reported to enhance the immune system.
- the plant also has anti-tumor properties (Ayaz and Alpsoy, Garlic ( Allium sativum ) and traditional medicine, Turkiye Parazitol Derg. 2007;31(2): 145-9). It houses many active molecules like allicin, saponins, phenolics and amino acids which are responsible for its biological activity.
- Allicin scavenges free radicals and inhibits NADPH oxidase. Allicin increases the production of 3 ⁇ 4S that results in hyperpolarisation of vascular smooth muscle cells causing vasodialation. Saponins, phenolics and s-allylcysteine directly quench the reactive oxygen species and elicit an anti-oxidant effect. The plant also produces arginine which is the precursor for the production of nitric oxide.
- the plant extract used in the instant invention is standardized using an in-house process to contain not less than 0.3% of s-allylcysteine.
- Beta vulgaris (Beet root) is a common vegetable used extensively along with normal diet. It also possesses excellent therapeutic properties which include hepatoprotection, anti-diabetic, hypocholesterolemic and hypolipidemic effects, anti-bacterial and anti-oxidant properties.
- the plant increases the enzyme called xanthine oxidoreductase (XOR) in the red blood cells which converts nitrate to nitrite, which is then turned into nitric oxide. Nitric oxide relaxes vessel walls and has an effect on blood pressure.
- XOR xanthine oxidoreductase
- Nitric oxide relaxes vessel walls and has an effect on blood pressure.
- the extract used in the present invention was standardized using an in-house process to contain not less than 2% nitrates.
- Nigella sativa is well known for its many therapeutic properties in the Ayruvedic, Siddha and Unani systems of medicine. The plant is reported to contain many active molecules like thymoquinone, thymohydroquinone, dithymoquinone, p-cymene, carvacrol, 4-terpineol, t- anethol, sesquiterpene longifolene, a-pinene, thymol, a hederin and hederagenin (Ahmad et al, A review on therapeutic potential of Nigella sativa: A miracle herb, Asian Pac J Trap Biomed.
- the plant is a well known anti-oxidant, cardiac-depressant and Calcium channel blocker which in turn affects the blood pressure and heart function.
- the extract used in the instant invention was standardized to contain 0.1% - 5% w/w thymoquinone, about 0.01% - 10% w/w thymohydroquinone, about 20% - 95% w/w fatty acids, about 0.001%- 3% w/w a-hederin or hederagenin.
- Terminalia arjima or arjuna is a well known medicinal plant used in the ancient Ayurvedic medicine.
- the bark of Terminalia arjuna is reported to contain many hioactive compounds, which can be tapped for use in the treatment of many diseases.
- Aqunoglucoside, a compound obtained from bark of Terminalia arjuna is well documented in literature for its cardio-protective activity.
- Terminalia arjuna and its bark extract reported for wide range of activities such as anticancer, hepatoprotective, antiviral, antioxidant, anti-asthmatic, anti-fertility, anti-diabetic, wound healing, anti-platelet and anticoagulant, anti -bacterial and anti-fungal activity.
- Table 1 discloses the details of the formulation and it dose.
- Kidney cell line, MDCK were seeded onto six-well plates at 30% confluence. Three days later, they were treated with 10 mM bradykinin (to increase endogenous PGE2synthesis, available in Sigma-Aldrich) in the presence of vehicle (DMSO) at 37°C for various durations.
- DMSO vehicle
- the formulation was added at graded concentration simultaneously to the cell culture and it was further incubated for 24 hours. Media were collected for measurements of extracellular concentrations of PGE2. Cells were washed with phosphate-buffered saline twice, lysed with 250 m ⁇ .
- PGE2 In cultured MDCK cells, the formulation blocks PGE2 uptake. PGE2 triggers a vast variety of signals including inflammation, vasodilation, and angiogenesis (Weeks JR (1972) Prostaglandins. Annu Rev Pharmacol 12:317-336; Clyman RI, Mauray F, Roman C, and Rudolph AM (1978) PGE2 is a more potent vasodilator of the lamb ductus arteriosus than is either PGI2 or 6 keto PGFlalpha.
- Prostaglandins 16:259-264; Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, and DuBois RN (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93:705-716.).
- the extent of PG signaling depends, to a large degree, on its concentration at cell-surface receptors, which is determined, in turn, by the relative rates of synthesis and metabolism and the transport of PG by Prostaglandin transporter.
- Cell media were collected for extracellular PGE2 measurements (Fig. 1), and cells were lysed for intracellular PGE2 measurements. Decreased level of extracellular PGE2 in the formulation treated cells (Fig. 2) shows that the Prostaglandin transporter was blocked and did not allow the PGE2 formed inside the cells to come out from cells to the media.
- Normotensive wistar rats were used for the experiments, The rats were spontaneously induced hypertension by the administration of DOCA (deoxycorticosterone acetate) a synthetic mmeralocorticoid derivative, 25mg/kg s.c. twice a week and 1% w/v NaCl in drinking water for a period of 30 days (Model : DOCA salt induced hypertension in rats). The rats were divided into the following groups containing 6 each:
- Solute carrier organic anion transporter family member 2A1 is also known as the prostaglandin transporter (PGT).
- PGT prostaglandin transporter
- Prostaglandin transporter is a member of the 12 -membrane- spanning organic anion-transporting polypeptide super family of transporters. The encoded protein is involved in mediating the uptake and clearance of prostaglandins in numerous tissues. The effect of the formulation was estimated in the plasma of the rats by ELISA.
- Tlie Blood Pressure, Heart Rate and Mean Arterial Pressure were estimated using standard protocol. Increase in salt, increased the levels of systolic and diastolic blood pressure, heart rate and Mean arterial pressure.
- the formulation by inhibiting PGT effectively lowered the Blood Pressure (Fig, 5A and 5B), Heart Rate (Fig. 6) and Mean Arterial Pressure (Fig. 7) in a dose dependant manner indicating that it is a very effective anti-hypertensive composition,
- the formulation comprising the plant extracts was very effective in inhibiting PGT thereby eliciting an anti-hypertensive effect.
- the formulation was effective in reducing the heart rate, systolic and diastolic blood pressure. Since elevated heart rate is related to the development of cardiovascular complications, the lowering of heart rate by the formulation through inhibition of PGT can confer a cardioprotective effect. Thus, the cardio protective effect by of the formulation was tested in Isoproterenol induced cardio-toxicity in rats.
- Isoproterenol [l-(3, 4-dihydroxyphenyl)-2-isopropylamino ethanol hydrochloride] (ISO), a synthetic catecholamine and b-adrenergic agonist, causes severe oxidative stress in the myocardium, resulting in infarct-like necrosis of the heart muscle. It is also known to generate free radicals and to stimulate lipid peroxidation. The following cardiac markers were evaluated: a) Aspartate aminotransferase (AST). b) Lactate dehydrogenase (LDH).
- AST Aspartate aminotransferase
- LDH Lactate dehydrogenase
- AST occurs in all human tissues and present in large amounts in liver, renal, cardiac and skeletal muscle tissue. The level increases in myocardial infarction, muscular dystrophy and liver diseases. The increase in the AST levels in the present invention indicates damage to the heart due to increased cardiotoxicity due to Isoproterenol. The formulation effectively reduced AST levels (Fig. 8) thereby indicated that it mitigates the cardiotoxicity developed due to increased salt intake. Similarly, the LDH and CK-MB levels (Fig. 9) also returned to normal in rats administered with the formulation, indicating its cardioprotective effects. [Para 0066] The results indicated that the formulation is an excellent PGT inhibitor.
- the formulation also conferred related therapeutic benefits of PGT inhibition by being an antihypertensive by reversing the increase in heart rate, blood pressure and Mean arterial pressure close to the normal levels.
- the formulation is also confers cardioprotective effects by decreasing the elevated cardiac markers close to near normal levels.
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