A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder e.

Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile.

Tablets may optionally be provided with an enteric coating, to provide release in parts of the gut other than the stomach. Pharmaceutical compositions for topical administration according to the present invention may be formulated as an ointment, cream, suspension, lotion, powder, solution, paste, gel, spray, aerosol or oil.

Alternatively, a formulation may comprise a patch or a dressing such as a bandage or adhesive plaster impregnated with active ingredients and optionally one or more excipients or diluents. Formulations suitable for topical administration in the mouth also include lozenges comprising the active ingredient in a flavored basis, usually sucrose and acacia or tragacanth; pastilles comprising the active ingredient in an inert basis such as gelatin and glycerin, or sucrose and acacia; and mouthwashes comprising the active ingredient in a suitable liquid carrier.

Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulations containing in addition to the active ingredient, such carriers as are known in the art to be appropriate.

Formulations suitable for nasal administration, wherein the carrier is a solid, include a coarse powder having a particle size, for example, in the range of about 20 to about microns which is administered in the manner in which snuff is taken, i. Suitable formulations wherein the carrier is a liquid for administration as, for example, nasal spray, nasal drops, or by aerosol administration by nebulizer, include aqueous or oily solutions of the active ingredient.

Formulations suitable for parenteral administration include aqueous and non-aqueous isotonic sterile injection solutions which may contain anti-oxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents, and liposomes or other microparticulate systems which are designed to target the compound to blood components or one or more organs.

The formulations may be presented in unit-dose or multi-dose sealed containers, for example, ampoules and vials, and may be stored in a freeze-dried lyophilized condition requiring only the addition of the sterile liquid carrier, for example water for injections, immediately prior to use.

Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described. Preferred unit dosage formulations are those containing a daily dose or unit, daily subdose, as herein above recited, or an appropriate fraction thereof, of a drug ingredient.

It should be understood that in addition to the ingredients particularly mentioned above, the formulations of this invention may include other bio-active agents conventional in the art having regard to the type of formulation in question.

For the purpose of illustration only, such additional bio-active agents include, but are not limited to sulphonylureas, e. chlorpropamide the trade name: Meldijan, etc.

and biguanides which includes, e. phenyl-ethyl-biguanide trade names: Phenformin, DB-Comb, etc. as well as dimethyl-biguanides trade names: Gluchopage, etc. In yet a further embodiment, additional agents suitable of oral administration may be included in the compositions and formulations, e.

The extract, fraction, compound or composition comprising one or more of the same, may also be presented for use in the form of veterinary formulations, which may be prepared, for example, by methods that are conventional in the art. This invention further provides a method for screening for a therapeutic agent for treating or ameliorating the symptoms associated with abnormal blood glucose, e.

In one aspect, the patient is suffering from diabetes Type II. The assay can also be used to screen new or alternative formulations or combinations of the extract with another active agent or therapeutic.

The screen requires a the administration of the potential agent to a suitable animal model and b administering an effective amount of the extract, or a pharmaceutically acceptable composition containing the extract, to another suitable animal.

The biomarkers of the therapeutic response of the animal s of step a to those of step b are compared. If any agent of step a provides a therapeutic response that is the same or similar extent as the model of step b , it is a therapeutic agent for treating or ameliorating the symptoms associated with abnormal blood glucose in an animal.

Suitable animal models include, but are not limited to the animal model described in Experiment No. or a human patient, e. Also provided is the use of the extract in the manufacture of a medicament for the treatment of diabetes.

A kit for treating or ameliorating the symptoms associated with abnormal blood glucose, e. The kit includes a therapeutically effective amount of the extract and instructions for use.

The kit is useful to treat disorders selected from the group consisting of Type II diabetes, abnormal steraroyl-CoA desaturase activity, hyperphagia, abnormal lipid mobilization, abnormal fatty acid profile from the eye of the subject, ulcers and glucosuria. The following examples are intended to illustrate, but not limit the invention.

Lipids constitute a major part of living cells where they provide the physical barrier that compartmentalizes cells and serve as a major storage form of energy in the liver and adipose tissue. Membrane lipids do not just form an inert framework for cells. Rather, fundamental roles are now recognized for membrane lipids and their bioactive derivatives in cell function, especially in the responses of the cell to external stimuli from hormones, neurotransmitters and growth factors.

It is therefore not surprising that alterations in membrane lipid composition have been associated with specific disease conditions such as cystic fibrosis Freedman et al. Vessby B. However, there are conflicting reports in the literature as to the extent of the alterations and as to which tissue or organs best manifest the modifications.

While increases in the saturated fatty acid SFA and the lower molecular weight polyunsaturated fatty acid PUFA contents have been associated with altered skeletal muscle insulin responsiveness in man, Clore et al. Arachidonic acid and a lower linoleic acid content in serum of diabetics as compared to samples taken from healthy controls.

In order to establish the status of some of the parameters associated with lipid homeostasis in Type II diabetes model mice, the fatty acid FA content of tissues implicated in the pathophysiology of diabetes in mice was investigated.

The tissues investigated for their FA profiles include adipose tissue, eye, liver, pancreas and skeletal muscle. The results show that while there was an accumulation of lipids in most of the different tissues from the obese mice, there was selectiveness in the deposition of lipids in the adipose tissue, eye and muscle of the diabetic mice, and suggested increase in stearoyl-CoA desaturase activity in the latter two tissues.

The study was performed under the guidelines approved by the Danish Animal Care and Use license. The animals were purchased from Bomholtgaard Breeding and Research Centre Ltd. The animals were kept in groups of mice per cage, maintained on Altromin standard maintenance diet and housed in a room kept at 25° C.

with a 12 h dark and 12 h light cycle. When the animals were 23 weeks old, they were fasted overnight. On the next day, the animals were weighed, ether anaesthetized and blood samples were collected by orbital puncture, before the animals were sacrificed.

The blood samples were allowed to clot at room temperature about an hour and cleared serum samples were collected after high-speed centrifugation g at 4° C.

for 30 min. Missouri, USA. Briefly, the apparatus was fitted with a 60 m fused silica capillary column SP and the injector and detector temperature were at ° C.

The carrier gas was helium. The initial oven temperature was 70° C. for 0. The activities of selected enzymes involved in fatty acid biosynthesis were estimated as the product to precursor ratios of the percentages of the individual fatty acids.

The estimated fatty acid-related metabolic processes included the delta9 or Stearoyl-CoA desaturase activity estimated as the ratio of oleic acid [C n-9 ] to stearic acid C ratio, and delta6 desaturase that was calculated as the ratio of the sum of γ-linolenic acid LNA, [C n-6 ], dihomogamalinolenic acid DGLA, [C n-6 ] and Arachidonic acid AA, [C n-6 ] to linoleic acid [C n-6 ].

The values are expressed as mean±standard errors. Statistical differences in the data were tested using ANOVA non-paired t-tests in Microsoft Excel.

The body weights, serum insulin and glucagon levels from the mice are presented in Table 1. There was no significant difference between the mean body weight of the diabetic mice and their lean counterparts. Genetically Obese and Diabetic Mice Tissues Differ in How Monounsaturated Fatty Acids are Accumulated.

The relative amounts of the major classes of fatty acids for the adipose tissue, eye, skeletal muscle, pancreas, liver-triacylglyceride liver-TAG fraction and liver-phospholipid liver-PL fraction from the different mice are presented in FIGS. Generally, there was an increase in the total fatty acids and in particular SFA and MUFA in the tissues from the obese mice, as compared to that in both the lean and diabetic mice tissues.

Thus, with the exception of the eye, significant increases in SFA and MUFA accumulation were observed in the obese mice tissues in comparison with values in the lean mice. Interestingly, the genetically diabetic mice only showed a significant increase in FA accumulation especially MUFA in adipose tissue, the skeletal muscle and in the eye, when compared to the FA content in the lean mice tissues FIG.

In line with the above observations of MUFA accumulation, there was an increase in the calculated stearoyl CoA desaturase activity in most of the tissues from the obese mice FIGS. For the diabetic mice, a significant increase in delta9 desaturation was only associated with the eye and skeletal muscle, which also had a marked accumulation of MUFAs see above.

Genetically Obese and Diabetic Mice Differ in How and in What Type of Polyunsaturated Fatty Acids are Accumulated in Tissues. While both the long and short chain forms of the PUFAs were accumulated in the obese mice tissues, the increase in the PUFA fraction in the diabetic mice muscle was mainly due to an accumulation of the short chain LA and alpha-linolenic acid FIG.

The reduction in delta6 desaturation could not be verified with an estimate of the delta4 desaturation calculated as the ratio of DHA [C n-3 ] to docosapentanoic acid DPA [C n-3 ], as several of the tissues from the diabetic mice lacked detectible levels of DPA.

However, the reduction in delta6 desaturation does coincide with significant reductions in DHA levels in the diabetic mice. In the obese mice, reductions in estimated delta6 activity were also calculated for the pancreas and liver-TAG fraction, while an increase was predicted for the adipose tissue and the liver-PL fraction FIGS.

The liver and adipose tissue constitute the major tissues for storage, processing and distribution of caloric fuels in mammals. Under normal conditions, there is a dynamic interplay between these and other tissues in the body that is highly responsive to certain hormones and co-factors, and ensures that mammalian tissues maintain a constant flow of energy-rich fuels despite intermittent fasting periods.

Type II diabetes or NIDDM results from a malfunction in the body's energy metabolism. The metabolic disturbances characteristic of NIDDM are increasingly being closely linked with alterations in lipid metabolism and obesity. Vessby New Eng. Obesity is characterised by an increased accumulation of tissue lipids.

Thus, the liver in severe mice diabetes appears to be spared against lipid accumulation. Instead, the excessively generated MUFA is deposited in other non-adipose tissue, such as the eye and muscle see Table 2. Saturated fatty acids such as palmitic acid C and stearic acid C are synthesised in mammalian cells by the enzyme complex, FA synthetase FAS which uses the building blocks generated by the rate limiting enzyme, acetyl CoA carboxylase.

Enoch et al. However, in the high fat-diet that is common in most developed nations, some of the excess fat that is consumed is not catabolized, but simply stored in tissues. Schmid et al. In this study, the estimated stearoyl-CoA desaturase activity was enhanced in the tissues with the exception of the eye from the obese mice.

In the diabetic mice, the increase in stearoyl-CoA desaturase activity was only associated with the eye and muscle namely in two of the tissues with increased MUFA accumulation. A central role for the enzyme in FA accumulation in obesity and in the development of Type II diabetes has been confirmed by the finding that the loss of one of the two mice SCD genes led to a reduction in body adiposity and resistance to diet-induced weight gain.

Ntambi et al. USA Rahman et al. Indeed the anti-Type II diabetes drugs, thiazolidinediones have been shown to exert part of their anti-diabetic effects via the PPARγ receptor by repressing SCD1 gene expression.

Kurebayashi et al. One of the long-term complications associated with NIDDM is poor wound healing. Today Essential fatty acids EFAs are important precursors for several eicosanoids and docosanoids that have pro-inflammatory and anti-inflammatory effects, respectively. Hence, the alterations in the EFAs in the two NIDDM model mice were examined.

In adult humans, insulin resistance in obesity and diabetes has been associated with relatively low proportions of the long chain PUFAs in skeletal tissue Borkman et al. The biosynthesis of the long chain essential PUFAs from LA and alpha-linolenic acid in mammalian cells is driven by the delta6 and delta5 desaturases in a series of enlongation and desaturation steps.

In the absence of insulin as is the case in untreated type I diabetes , both enzyme activities are down regulated. Brenner Prostaglandins Leukot. Fatty Acids The condition is corrected on administration of insulin.

Mercuri et al. Although the activity of the enzymes have been well studied in type I diabetes, there is a paucity of data concerning their levels and activities in Type II diabetes.

Furthermore, the lack of distinction between triacylglycerol and phopholipid fractions in most of the tissues analysed here makes it difficult to ascertain whether the increases in LA or alpha-linolenic are simply due to increases in triacylglycerol that favours accumulation of the short chain PUFAs.

Nevertheless, the alterations in the tissue content of EFAs in Type II diabetes can have some far reaching effects for the prognosis of Type II diabetes.

On the one hand, the long chain PUFA DHA that is scarce in severe NIDDM, is one of the main precursors for docosatrienes and resolvins that are beneficial for the resolution of both acute and chronic inflammation Hong et al. Calder Ann. On the other hand, a lipid based-molecule derived from LA by the action of lipoxygenase-1, S-hydrocyoctadecadienoic acid has been shown to be an apoptotic agent.

Shureiqi et al. USA ; Nixon et al. Taken together, the reduction in DHA combined with the increase in LA might contribute to enhancing some of the long-term complications of diabetes associated with the eye and in poor wound healing in skeletal muscle. Recently, Brenner and associates Brenner et al.

FA metabolism is cell-specific and the both the stearoyl CoA desaturase and delta6 desaturase activities considered in this study are estimates.

It is therefore interesting to determine and compare the actual levels of expression and activities of the enzymes involved in the lipid homeostasis in tissues taken from the 3 groups of C57BL mice. There were clear differences in lipid contents and composition in the tissues from the lean, obese and diabetic mice based on the same C57BL-genotype and fed the same diet.

Thus, with the exception of the eye, there was an accumulation of SFA and MUFA in all tissues from the genetically obese mice. The liver was spared the lipid accumulation and fatty acids-build up of the MUFA subclass was restricted to the eye, adipose tissue and skeletal muscle.

Both the mild and severe forms of NIDDM were associated with PUFA accumulation in the skeletal muscle, although the short chain PUFAs were predominantly responsible for the increases in severe NIDDM. These distortions in the tissue lipids in Type II diabetes may define the pathophysiology of the disease.

Experiment No. Plant material and preparation of the Rauvolfia - Citrus infusion. A combination of washed dried foliage total weight, g was arranged in alternate layers with quartered whole citrus fruits total wet weight 2 kg , in a large aluminium pot.

The plant material was then covered with 8 liters of tap water, brought to the boil, and allowed to simmer covered, at low heat for 1 h. The resulting golden coloured fluid was cooled to room temperature and filtered through coarse filters.

The total yield was typically 7. The pooled plant extract was freeze-dried and the yield was typically 12 g dried extract from 1 liter. The mice are characterised by obesity, hyperphagia, temporal hyperinsulinaemia, degeneration of the pancreatic β-cells with age and hyperglycemia. Due to the insulin resistance observed in these mice, they are considered models of Type II non-insulin dependent diabetes.

The db gene has been identified as coding for one of the different mice forms of leptin receptors expressed in the hypothalamus. Lee et al.

Objective: In this study, the effect of short-term consumption of sour orange juice on blood glucose and lipid profile of diabetic patients was evaluated. Materials and Methods: In a clinical trial study before and after , thirty-five 10 men and 25 women dyslipidemic diabetic patients without nephropathy with mean age Each patient consumed ml of sour orange juice daily for 4 weeks.

The patients were asked to maintain their usual diet, physical activity and consumption of their oral hypoglycemic agent during the entire experimental period. Body weight and height were measured at baseline and after consumption of ml of sour orange juice daily for four weeks and BMI was calculated.

Fasting blood glucose, lipids and ascorbic acid level were measured at the beginning and the wnd of the study. Plasma ascorbic acid concentrations were measured by the 2,4 dinitrophenyl hydrazine method with calorimetric analysis. FBS, TG, and total cholesterol were measured by enzymatic method.

A 24 hr dietary recall and food frequency questionnaire were analyzed by Nutrition III soft ware. However, more rigorous human research is needed An ongoing study is also exploring the use of limonene as a treatment for COVID However, the results are not yet known.

Bear in mind that limonene cannot prevent or cure COVID Another protoalkaloid found in bitter orange is p-octopamine. However, little to no p-octopamine exists in bitter orange extracts.

The leaves of the bitter orange plant are rich in vitamin C , which acts as an antioxidant. Antioxidants are substances that may protect your body from disease by preventing cell damage. They work by deactivating free radicals, which are unstable compounds that damage your cells, increasing inflammation and your disease risk 15 , Protoalkaloids are plant compounds found in bitter orange that have anti-inflammatory and antiviral properties.

They have been shown to be safe for consumption. Many weight loss supplements use bitter orange extracts in combination with other ingredients. However, scientific studies have not thoroughly examined the composition of these supplements to determine which ingredient, if any, supports weight loss.

Notably, p-synephrine has been shown to increase fat breakdown, raise energy expenditure, and mildly suppress appetite , all of which may contribute to reduced weight.

Yet, these effects occur at high doses that are discouraged due to the lack of safety information 4 , 8 , Bitter orange and its extracts are used in Traditional Chinese Medicine TCM to treat indigestion, diarrhea, dysentery, and constipation. In other regions, the fruit is used to treat anxiety and epilepsy 3.

Another study noted that the bitter orange compound p-synephrine may improve athletic performance though by increasing total reps and volume load, or your ability to train harder A stimulant is a substance that increases your heart rate and blood pressure 1.

Several sports organizations, such as the National Collegiate Athletic Association NCAA , list synephrine as a stimulant. Furthermore, one study determined that bitter orange juice contains furanocoumarin, a compound that may cause the same medication interactions as grapefruit juice Therefore, people taking decongestants or those who have high blood pressure, an irregular heartbeat, or glaucoma should avoid the juice and fruit of bitter oranges.

Despite numerous studies showing that bitter orange extracts are not stimulants, widespread controversy exists, and the NCAA has listed it as a banned substance.

Bitter orange may also interact with certain medications. Generally, bitter orange extracts in dietary supplements are safe to consume in doses of 50—98 mg per day 1 , One study showed that 40 mg of synephrine combined with mg of caffeine is a safe dose of these combined ingredients 3.

In another study, eating a whole bitter orange containing Still, people who are pregnant or breastfeeding should avoid bitter orange due to a lack of safety information 1.

Bitter orange is likely safe in doses ranging from The juice of the bitter orange can be used as a marinade to flavor fish and meat. Bitter orange has several other household uses outside of the kitchen.

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We would like to thank Dr. Ramkumar, Vice Principal, Ultra College of Pharmacy, Madurai for his valuable suggestions for the completion of this research work. Department of Biochemistry, Sri Sarada Niketen College for Women, Amaravathipudur, affiliated to Alagappa University, Karaikudi, Tamil Nadu, India.

Department of Botany, Arumugam Pillai Seethai Ammal College, Thiruppathur, affiliated to Alagappa University, Karaikudi, Tamil Nadu, India.

PG and Research Department of Botany, Raja Doraisingam Government Arts College, Sivagangai, affiliated to Alagappa University, Karaikudi, Tamil Nadu, India.

PG and Research Department of Botany, Pasumpon Thiru Muthuramalingam Memorial College, Kamuthi, affiliated to Alagappa University, Karaikudi, Tamil Nadu, India.

Centre for Research in Botany, Saraswathi Narayanan College Madurai, affiliated to Madurai Kamaraj University, Chennai, Tamil Nadu, India. You can also search for this author in PubMed Google Scholar.

SRS designed and outlined the study. BP supervised the collection of plant materials and carried out the determinations. ES and UV performed HPTLC analysis. VN drafted and revised the manuscript. All authors have approved the manuscript for submission.

Correspondence to Vijayanand Narayanan. We would like to state that a written consent and approval has been obtained from the institution to use the animals for this study. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Reprints and permissions. Ramya, S. et al. Potential of peel extracts of Punica granatum and Citrus aurantifolia on alloxan-induced diabetic rats. Beni-Suef Univ J Basic Appl Sci 9 , 24 Download citation. Received : 17 September Accepted : 03 April Published : 16 June Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all SpringerOpen articles Search. Download PDF. Abstract Background Peel is one of the major by-products in fruit processing industry.

Results Among the different solvent extracts, methanol solvent extract was found to possess more amounts of secondary metabolites.

Conclusion It can be concluded that fruit peels of both the plants exhibited antidiabetic potential on alloxan-induced diabetic rats which can be attributed to wide range of active pool of secondary metabolites. Graphical abstract. Table 1 Phytochemical screening of extracts of fruit peel of Citrus aurantifolia and Punica granatum Full size table.

Full size image. Table 2 Effect of methanolic peel extracts of Punica granatum on biochemical parameters of alloxan-induced diabetic rats Full size table. Table 3 Effect of methanolic peel extracts of Citrus aurantifolia on biochemical parameters of alloxan-induced diabetic rats Full size table.

Abbreviations HPTLC: High Performance Thin Layer Chromatography GLUT4: Glucose transporter type 4 TLC: Thin layer chromatography RF: Retardation factor UV: Ultraviolet HDL: High density lipoprotein LDL: Low density lipoprotein MKU: Madurai Kamaraj University IAEC: Institutional Animal Ethical Committee KMCP: K.

College of Pharmacy TNAU: Tamil Nadu Agricultural University. References Aubert RE, Hilary KWH Global Burden of Diabetes, Diabetes Care — Google Scholar Wen J, Zhang JQ, Huang W, Wang Y SDF-1α and CXCR4 as therapeutic targets in cardiovascular disease. Am J Cardiovasc Dis — Google Scholar Stein SA, Lamos EM, Davis SN A review of the efficacy and safety of oral antidiabetic drugs.

J Sci Enviroment Technol — Google Scholar Park J, Lee M, Park E Antioxidant activity of orange flesh and peel extracted with various solvents. Prev Nutr Food Sci 19 4 — Article Google Scholar Gamble JS The flora of the presidency of Madras.

Pvt Ltd, New Delhi Google Scholar Trease GE, Evans WC Pharmacognosy, W. Spectrum Books Ltd, Ibadan, pp — Google Scholar Sethi PD High performance thin layer chromatography HPTLC. CBS Publishers, New Delhi, pp 3—62 Google Scholar Thomson EB Drug bioscreening: fundamentals of drug evaluation techniques in pharmacology.

x Article CAS PubMed Google Scholar Lorke D A new approach to practical acute toxicity testing. Arch Toxicol — Article CAS Google Scholar Trinder P Determination of blood glucose using an oxidase-peroxidase system with a non carcinogenic chromogen.

Orient Longman, Hyderabad Google Scholar Zlatkis A, Zak B, Boyle AJ A new method for the direct determination of serum cholesterol. Pract Clin Biochem Google Scholar Middha SK, Usha T, Pande V , A review on antihyperglycemic and antihepatoprotective activity of eco-friendly Punica granatum peel waste.

doi: PDF KB. Effects of Citrus aurantium on kidney antioxidant function and islet in experimental diabetic mice. Received Date: Publish Date: Objective To study the effect of Citrus aurantium C.

aurantium extract on kidney antiox idantability and islet in experimental diabetic mice. Methods Experimental diabetic mice were treat with C. aurantium extract 1. After 4 weeks,the general status,kidney antio xidant ability and morphological change of islet were observed. Results The blood glucose of diabetic mice treated with high dose of C.

aurantium extract was significantly lower that of untreated mice aurantium can effectively enhance the kidney an tioxidant function and decrease islets cell damages. FullText HTML.

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