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  <journal-meta>
   <journal-id journal-id-type="publisher-id">Foods and Raw Materials</journal-id>
   <journal-title-group>
    <journal-title xml:lang="en">Foods and Raw Materials</journal-title>
    <trans-title-group xml:lang="ru">
     <trans-title>Foods and Raw Materials</trans-title>
    </trans-title-group>
   </journal-title-group>
   <issn publication-format="print">2308-4057</issn>
   <issn publication-format="online">2310-9599</issn>
  </journal-meta>
  <article-meta>
   <article-id pub-id-type="publisher-id">50716</article-id>
   <article-id pub-id-type="doi">10.21603/2308-4057-2022-2-532</article-id>
   <article-categories>
    <subj-group subj-group-type="toc-heading" xml:lang="ru">
     <subject>Research Article</subject>
    </subj-group>
    <subj-group subj-group-type="toc-heading" xml:lang="en">
     <subject>Research Article</subject>
    </subj-group>
    <subj-group>
     <subject>Research Article</subject>
    </subj-group>
   </article-categories>
   <title-group>
    <article-title xml:lang="en">Formulating anti-diabetic nutraceutical tablets based on edible plants from Tripura, India</article-title>
    <trans-title-group xml:lang="ru">
     <trans-title>Formulating anti-diabetic nutraceutical tablets based on edible plants from Tripura, India</trans-title>
    </trans-title-group>
   </title-group>
   <contrib-group content-type="authors">
    <contrib contrib-type="author">
     <contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9698-0012</contrib-id>
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Debnath</surname>
       <given-names>Bikash </given-names>
      </name>
      <name xml:lang="en">
       <surname>Debnath</surname>
       <given-names>Bikash </given-names>
      </name>
     </name-alternatives>
     <xref ref-type="aff" rid="aff-1"/>
    </contrib>
    <contrib contrib-type="author">
     <contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5327-365X</contrib-id>
     <name-alternatives>
      <name xml:lang="ru">
       <surname>Manna</surname>
       <given-names>Kuntal </given-names>
      </name>
      <name xml:lang="en">
       <surname>Manna</surname>
       <given-names>Kuntal </given-names>
      </name>
     </name-alternatives>
     <email>k_manna2002@yahoo.com</email>
     <xref ref-type="aff" rid="aff-2"/>
    </contrib>
   </contrib-group>
   <aff-alternatives id="aff-1">
    <aff>
     <institution xml:lang="ru">Tripura University (A Central University)</institution>
     <city>Suryamaninagar</city>
     <country>Индия</country>
    </aff>
    <aff>
     <institution xml:lang="en">Tripura University (A Central University)</institution>
     <city>Suryamaninagar</city>
     <country>India</country>
    </aff>
   </aff-alternatives>
   <aff-alternatives id="aff-2">
    <aff>
     <institution xml:lang="ru">Tripura University (A Central University)</institution>
     <city>Suryamaninagar</city>
     <country>Индия</country>
    </aff>
    <aff>
     <institution xml:lang="en">Tripura University (A Central University)</institution>
     <city>Suryamaninagar</city>
     <country>India</country>
    </aff>
   </aff-alternatives>
   <pub-date publication-format="print" date-type="pub" iso-8601-date="2022-09-23T06:16:30+03:00">
    <day>23</day>
    <month>09</month>
    <year>2022</year>
   </pub-date>
   <pub-date publication-format="electronic" date-type="pub" iso-8601-date="2022-09-23T06:16:30+03:00">
    <day>23</day>
    <month>09</month>
    <year>2022</year>
   </pub-date>
   <volume>10</volume>
   <issue>2</issue>
   <fpage>227</fpage>
   <lpage>234</lpage>
   <history>
    <date date-type="received" iso-8601-date="2021-10-29T00:00:00+03:00">
     <day>29</day>
     <month>10</month>
     <year>2021</year>
    </date>
    <date date-type="accepted" iso-8601-date="2022-05-05T00:00:00+03:00">
     <day>05</day>
     <month>05</month>
     <year>2022</year>
    </date>
   </history>
   <self-uri xlink:href="https://jfrm.ru/issues/20341/20336/">https://jfrm.ru/issues/20341/20336/</self-uri>
   <abstract xml:lang="ru">
    <p>Nutraceuticals are food-based drugs that are used as dietary supplements to minimize chronic diseases. Diabetes is one of the most common chronic diseases all over the world. Recently, herbal nutraceuticals have taken a promising role in treating diabetes.&#13;
We aimed to develop herbal nutraceutical tablets and evaluate its anti-diabetic activity using ob/ob mice. Five plant species were collected by field survey methods based on oral interviews with traditional healers of Tripura. The wet granulation method was applied to formulate the herbal nutraceutical tablet. Water- and fat-soluble vitamins were determined by reversed-phase highperformance liquid chromatography. Trace elements were analyzed by atomic absorption spectrophotometry. To evaluate the anti-diabetic activity of the herbal tablets, we determined serum hemoglobin, glycosylated serum protein, and oral glucose tolerance.&#13;
The newly formulated herbal nutraceutical tablets provided the optimal energy level. It contained sufficient amounts of essential minerals, such as iron (74.6 ± 2.7 mg/g), sodium (4.4 ± 0.4 mg/g), potassium (5.3 ± 0.7 mg/g), calcium (163.1 ± 2.2 mg/g), magnesium (39.2 ± 1.7 mg/g), and phosphorus (14.6 ± 2.1 mg/g). We also found optimal quantities of water-soluble vitamins, such as vitamin C (27.2 ± 4.3 mg/g), vitamin B1 (0.6 ± 0 mg/g), vitamin B3 (0.6 ± 0.2 mg/g), vitamin B6 (1.1 ± 0.2 mg/g), vitamin B12 (0.6 ± 0.2 μg/g), and folic acid (82.6 ± 7.6 μg/g), as well as fat-soluble vitamins, such as vitamin A (287.4 ± 6.3 μg/g), vitamin D3 (2.6 ± 0.6 μg/g), and vitamin E (0.7 ± 0 ng/g). Finally, the herbal nutraceutical tablet (200 mg/kg) significantly improved the antihyperglycemic effect on ob/ob mice (type 2 diabetes), compared to the standard drug, metformin (200 mg/kg).&#13;
The results suggest that the newly formulated herbal tablet may be recommended as an anti-diabetic nutraceutical drug.</p>
   </abstract>
   <trans-abstract xml:lang="en">
    <p>Nutraceuticals are food-based drugs that are used as dietary supplements to minimize chronic diseases. Diabetes is one of the most common chronic diseases all over the world. Recently, herbal nutraceuticals have taken a promising role in treating diabetes.&#13;
We aimed to develop herbal nutraceutical tablets and evaluate its anti-diabetic activity using ob/ob mice. Five plant species were collected by field survey methods based on oral interviews with traditional healers of Tripura. The wet granulation method was applied to formulate the herbal nutraceutical tablet. Water- and fat-soluble vitamins were determined by reversed-phase highperformance liquid chromatography. Trace elements were analyzed by atomic absorption spectrophotometry. To evaluate the anti-diabetic activity of the herbal tablets, we determined serum hemoglobin, glycosylated serum protein, and oral glucose tolerance.&#13;
The newly formulated herbal nutraceutical tablets provided the optimal energy level. It contained sufficient amounts of essential minerals, such as iron (74.6 ± 2.7 mg/g), sodium (4.4 ± 0.4 mg/g), potassium (5.3 ± 0.7 mg/g), calcium (163.1 ± 2.2 mg/g), magnesium (39.2 ± 1.7 mg/g), and phosphorus (14.6 ± 2.1 mg/g). We also found optimal quantities of water-soluble vitamins, such as vitamin C (27.2 ± 4.3 mg/g), vitamin B1 (0.6 ± 0 mg/g), vitamin B3 (0.6 ± 0.2 mg/g), vitamin B6 (1.1 ± 0.2 mg/g), vitamin B12 (0.6 ± 0.2 μg/g), and folic acid (82.6 ± 7.6 μg/g), as well as fat-soluble vitamins, such as vitamin A (287.4 ± 6.3 μg/g), vitamin D3 (2.6 ± 0.6 μg/g), and vitamin E (0.7 ± 0 ng/g). Finally, the herbal nutraceutical tablet (200 mg/kg) significantly improved the antihyperglycemic effect on ob/ob mice (type 2 diabetes), compared to the standard drug, metformin (200 mg/kg).&#13;
The results suggest that the newly formulated herbal tablet may be recommended as an anti-diabetic nutraceutical drug.</p>
   </trans-abstract>
   <kwd-group xml:lang="ru">
    <kwd>Edible medicinal plant</kwd>
    <kwd>herbal nutraceutical</kwd>
    <kwd>tablet dosage</kwd>
    <kwd>anti-diabetic activity</kwd>
    <kwd>dietary supplement</kwd>
   </kwd-group>
   <kwd-group xml:lang="en">
    <kwd>Edible medicinal plant</kwd>
    <kwd>herbal nutraceutical</kwd>
    <kwd>tablet dosage</kwd>
    <kwd>anti-diabetic activity</kwd>
    <kwd>dietary supplement</kwd>
   </kwd-group>
   <funding-group>
    <funding-statement xml:lang="ru">The authors are grateful to the Indian Council of Medical Research (ICMR) (No. 3/1/2/125/2019-Nut) and the All- India Council for Technical Education (AICTE) (No. 8-114/RIFD/RPS-NER/Policy-1/2018-19) for providing financial support.</funding-statement>
    <funding-statement xml:lang="en">The authors are grateful to the Indian Council of Medical Research (ICMR) (No. 3/1/2/125/2019-Nut) and the All- India Council for Technical Education (AICTE) (No. 8-114/RIFD/RPS-NER/Policy-1/2018-19) for providing financial support.</funding-statement>
   </funding-group>
  </article-meta>
 </front>
 <body>
  <p>INTRODUCTIONModern lifestyle involves changes in essentialfood habits [1]. Due to improper diet, people sufferfrom various kinds of chronic diseases. Obesity, heartdisease, and diabetes are among current global issues [2].Nutraceuticals are food-based drugs which minimizediet-related illnesses. The word “nutraceutical” comesfrom “nutrition” and “pharmaceutical” [3]. Anypharmaceutical product manufactured from foodsources has fundamental nutritional values and minimizesvarious chronic diseases [4].Recently, nutraceuticals have gained extensiveattention due to their better pharmacological functionswith fewer side effects. In 2017, 77% of Americansused nutraceuticals, and their number was risingdaily [5]. Nutraceuticals are classified as dietary fiber,probiotics, prebiotics, polyunsaturated fatty acids,antioxidant, vitamins, polyphenols, and spices [6].Herbal nutraceuticals are prepared from plants, fungi,algae, or their combinations. Various forms of herbalnutraceuticals (powder, tablets, capsules, liquid, etc.) arecurrently available in the market [7].About 2500 years ago, Hippocrates wrote, “Letfood be thy medicine and medicine be thy food.” Thisquotation is undoubtedly the principle of today [6]. Thenutraceutical industry has great potential in some AsianFoods and Raw Materials. 2022;10(2)ISSN 2310-9599 (Print)ISSN 2308-4057 (Online)228Debnath B. et al. Foods and Raw Materials. 2022;10(2):227–234countries, such as China, Japan, India, South Korea,Thailand, Singapore, and Taiwan. With rich naturalresources, skilled human resources, and excellent R&amp;Dfacilities, these Asian countries are expected to lead theproduction of herbal nutraceuticals [8, 9].Tripura is India’s state located in the northeasternpart of the subcontinent between 22o7’ and 24o2’ northlatitudes and 91o0’ and 92o0’ east longitudes. Its highesttemperature is 35.60°C, and yearly rainfall is 2000 mm.These excellent climatic conditions make Tripura afavorable place for various edible medicinal plants, orplants with nutritional benefits and bioactive compoundsfor the human body [10, 11].According to literature, the forest of Tripura is agood source of edible medicinal plants with anti-diabeticproperties [12]. Diabetes is a big issue in the Indianhealth care system. Type 2 diabetes is the most commonin adults with uncontrolled diet. Every year, nearly1 million Indians die due to diabetes. This chronicdisease afflicts 2.8% of the global population [13].Treatment with herbal medicine improves insulinsecretion and reduces intestinal glucose absorption indiabetics [14].This study aimed to formulate herbal nutraceuticaltablets from selected edible medicinal plants of Tripura,India, and evaluate its anti-diabetic activity using ob/obmice (type II diabetes model).STUDY OBJECTS AND METHODSEthnomedicinal data collection. Ethnomedicinaldata about five edible plant parts (Musa paradisiacafruit, Musa paradisiaca stem, Cmorphophalluspaeoniifolius corn, Artocarpus heterophyllus seed, andColocasia esculenta leaf) were collected from oralinterviews with traditional healers from three ethniccommunities (Tripuri, Reang, and Jamatia) of Tripura.All the interviewees were adults aged over forty [15].The scientific names of the collected plant specimenswere identified with the help of a plant taxonomist andthe book, “The Flora of Tripura State” [16].Processing of plant materials. After identification,we selected plant parts with medicinal properties,washed them thoroughly with distilled water, and thenproperly air-dried them. The dried samples were groundto fine powder. The powder material was packed in asealed container and preserved at room temperature forfurther experiments [17].Experimental animals. In our experiments, weused laboratory mice as model organisms. Adult Swissalbino mice (18–25 g) of both sexes were used foracute toxicity tests. Male ob/ob mice (type II diabetesmice weighing 50–55 g, aged 12 weeks) and maleC56BL6 mice (normal mice weighing 28–32 g, aged12 weeks) were used for an anti-diabetic activitytest. The temperature (20°C) and humidity (53%) ofthe animal house were controlled and maintainedthroughout the 12 h/12 h light/dark cycle. Food andwater were available except during the fasting period.The care and handling of the animals were in line withthe regulations of the National Institutes of Health. TheInstitutional Ethics Committee (No. 1667/GO/a/12/CPCSEA) approved the study protocol [18].Acute toxicity test. Acute toxicity tests of fivedifferent plant powder samples were measured bythe method described by Ali et al. with some modification[19]. The Swiss albino mice (18–25 g) of bothsexes were divided into two groups, the control groupand the experimental group, ten animals in each. Thecontrol group received only distilled water, whereasthe experimental group received different doses (5, 50,300, 800, 1200, and 2000 mg/kg body weight) of thepowder sample orally. The mice were then kept underobservation up to 72 h for mortality or symptoms oftoxicity [19].Formulation of herbal tablet. We used the wetgranulation method to prepare novel herbal antidiabeticnutraceutical tablets. Equal amounts ofpreviously prepared plant materials (M. paradisiacafruit, M. paradisiaca stem, C. paeoniifolius corn,A. heterophyllus seed, and C. esculenta leaf) were placedin a rapid mixture granulator, with a 10% starch solutionadded dropwise into the binder. The damp masseswere screened through a sieve #10 and then dried. Thedried granules were screened through a sieve #20 andstored in a desiccator until they were ready for tabletcompression. The prepared granules were compressed ina single punch tablet press machine (Manesty Type F3,Liver Poole, England) with a punch diameter of 0.75 cmand a compression pressure of 933 Pa (N/m2). The dievolume matched the tablets’ weight to confirm that600 mg was obtained [20].Evaluation of granules. Tablet granules wereevaluated by Wadher et al. methods with somemodification. Particularly, we determined their bulkdensity, tapped density, Hausner quotient, Carr’scompressibility index, flow rate, and angle of repose [21].Evaluation of herbal tablets. Weight variation,thickness, hardness, friability, and in vitro disintegrationtime were determined by Wadher et al. methods withsome modification [21].Total moisture, total carbohydrate, complete protein,total fat, total ash, and total caloric value of the herbaltablets were determined by Debnath et al. method withsome modification [17]. Total dietary fiber was measuredby Ozoliņa et al. method with some modification [22].Concentrations of minerals were determined by anatomic absorption spectrophotometer. Debnath et al.method with some modification was applied to measurethe content of minerals in the tablets [17].Vitamins C, B1, B3, B6, and folic acid weredetermined by Antakli et al. method with somemodification, using the RP-HPLC system [23].Instrumental conditions:Column: C18 BDS (10 cm×4.6 mm; 3 μm);Mobile phase: A = Hexane-1-sulfonic acid sodium(5.84 mM): acetonitrile (95:5) with 0.1% triethylamineas solvent (A) at pH 2.5; B = 5.84 mM of hexane-1-229Debnath B. et al. Foods and Raw Materials. 2022;10(2):227–234sulfonic acid sodium: acetonitrile (50:50) with 0.1%triethylamine as solvent (B) at pH 2.5, pH = 3.54;Flow rate: 1.6 mL/min;Injected volume: 20 μL;Absorbance recorded: Vitamins C and B1 = 246 nm,vitamin B3 = 260 nm, vitamin B6 = 290 nm, vitamin B9 == 282 nm.Determination of fat-soluble vitamins. Vitamins A,D3, and E were determined by using the reversed-phasehigh-performance liquid chromatography as reported byXue et al. with some modification [24].Instrumental conditions:Column: dC18 (particle diameter 5 μm, 150×4.6 mm i.d.);Mobile phase: methanol:water = 98:2;Flow rate: 1.00 mL/min;Injected volume: 10 μL;Absorbance recorded: vitamin E = 230 nm, vitaminA and D3 = 265nm.Anti-diabetic activity. Experimental design. Theanimals were randomly divided into four groups of sixanimals for test purposes, namely: a) a normal group(completely healthy mice) treated with 0.5% sodiumcarboxymethyl cellulose; b) a vehicle control group(ob/ob mice) treated with 0.5% sodium carboxymethylcellulose; c) a positive control group treated with 200mg/kg of metformin via gavage; and d) an experimentalgroup treated with 200 mg/kg herbal nutraceuticaltablet via gavage. The experiment lasted four weeks. Atthe end of the experiment, all the animal groups fastedovernight, and blood samples were collected from thetail vein. Before blood collection, the animals weregiven pentobarbital as an anesthetic agent [18].Determination of serum hemoglobin andglycosylated serum protein. Hemoglobin (HbA1c) andglycosylated serum protein were measured by respectivekits (Merck Millipore, Germany) according to themanufacturer’s instruction [18].Oral glucose tolerance test. After four weeks oftreatment with herbal nutraceutical tablets, the animalswere made to fast overnight, and glucose solution(2 g/kg of body weight) was administered orally. Afterthat, their blood samples were collected every 30 min(0, 30, 60, 90, and 120 min). The blood glucose wasmeasured by a glucose meter (i-QARE DS-W®) [18].Statistical analysis. For the analysis of granules,herbal tablets, proximate compositions, minerals, andvitamins, the data were expressed as mean ± SDs. Forthe evaluation of anti-diabetic activity in ob/ob mice,the data were expressed as mean ± S.E.M. One-wayANOVA was used to determine significant differencesamong groups, after which the modified Student’st-test with the Bonferroni correction was applied tocompare individual groups. All statistical analyseswere performed with SPSS 17.0 software. P &lt; 0.05 wasconsidered statistically significant.RESULTS AND DISCUSSIONEthnomedicinal study. The field survey showedthat the five edible medicinal plants were applied bythe healers of Tripura to cure different diseases (Table1). Ethnomedicinal studies play a vital role in findingmedicinal plants that can be used to produce novelcrude drugs. They also verify the protection of culturalheritage [11]. The data that we collected from theinformants of healers clearly proved that the plants wehad selected were of medicinal importance.Acute toxicity test. Our results indicated no changesof behaviour or mortality caused by the plant samplesat the highest dose of 2000 mg/kg b.wt. This meantthat this dose had no lethal or toxic effect. Toxicityassessment is one of the crucial steps prior to humanuses of any pharmaceuticals or food ingredients. Acutetoxicity studies determine adverse effects of any activecompound after oral ingestion of a single or multipledoses [19]. We found that the five plant samples understudy had no toxic effect.Evaluation of granules. All the physical parametersof the herbal granules under study were found to besatisfactory (Table 2). The Carr’s compressibility indexindicates the strength of the powder/granules, whilethe Hausner ratio determines the powder/granules’inter-particulate friction. Both parameters are usedto analyze the powder/granules’ flow rate. The Carr’scompressibility index of less than 10 or the Hausnerratio of less than 1.11 indicate an “excellent” flow rate,while the Carr’s compressibility index higher than 38 orthe Hausner ratio higher than 1.60 indicate a “very poor”flow rate. Both parameters depend on the bulk densityand the tap density of the powder/granules [25]. Theangle of repose is another parameter used to evaluatethe powder/granules’ flow rate. Its value of less than30° indicates an “excellent” flow rate, while the valuegreater than 56° indicates a “very poor” flow rate [26].Table 1 Ethnomedicinal use report on edible medicinal plant parts selectedBotanical name and family Local name Plants parts Ethnomedicinal useMusa paradisiaca (Musaceae) Kola Unripe fruit Diabetes, hypertension, ulcers, diarrheaMusa paradisiaca (Musaceae) Kola Stem Diabetes, high blood pressure, high acidityCmorphophallus paeoniifolius(Araceae)Batama Corn Helminths, liver disease, digestive and gastric disorders,diabetesArtocarpus heterophyllus(Moraceae)Kathal Seed Ulcers, constipation, diarrhea; excessive accumulationof fluid in tissuesColocasia esculenta (Araceae) Kocho Leaf Diabetes, microbial infection, liver disease230Debnath B. et al. Foods and Raw Materials. 2022;10(2):227–234Our results showed an excellent flow rate in the granulesprepared with a 10% starch solution (Table 2).Evaluation of herbal tablets. All the physicalparameters of the herbal tablets under study were foundto be satisfactory (Table 3). The weight variation test isemployed to ensure that each tablet/capsule in the batchcontains the same amount of drug ingredients. Checkinga tablet’s thickness is necessity for packaging since verythick tablets are not suitable for packaging. A tablet’sfriability and hardness tests are closely related to eachother. They determine the physical strength of a tablet.Disintegration refers to the mechanical breakup of acompressed tablet into small granules at a specific timepoint. The disintegration test provides critical safetydata on the drug’s bioavailability in the body [27, 28].In our experiments, 20 tablets were used to checkthe average uniformity of weight and 10 tablets to checkthe average uniformity of thickness and hardness. Forthe friability and disintegration tests, the samples wereprepared in triplicate. According to the results (Table 3),the physical parameters of our newly formulated tabletswere within the limits established by the United StatesPharmacopoeia.Determination of proximate composition. Theproximate composition of the herbal nutraceuticaltablets is represented in Table 4. The moisture content isan essential parameter because high moisture affects thephysical stability of food products. Their shelf life alsodepends on the total moisture content [29]. As we cansee in Table 4, our newly formulated herbal tablets hada low moisture content (62.44 ± 2.11 %), indicating highphysical stability.Carbohydrates, proteins, and fats hold a special placein human nutrition. The human body requires them inrelatively large amounts for normal functioning. Thesethree macronutrients provide energy (measured incalories) in the human body [30]. Our newly formulatedherbal nutraceutical tablet contained optimal amounts ofcarbohydrates (1.88 ± 0.52 %), proteins (0.95 ± 0.65 %),and fats (0.43 ± 0.53 %), as well as provided a goodamount of energy (15.19 kcal).So, the herbal nutraceutical tablets developed maybe recommended to people with unbalanced energylevels. Dietary fiber is a complex mixture of polysaccharides.Diets with a high content of fiber alleviateconstipation [31]. Our herbal nutraceutical tabletcontained a good amount of dietary fiber (1.66 ± 0.67%),so it may be used to reduce constipation.Minerals determination. Iron is an essentialmicroelement for producing blood. Anemia is themost common disease caused by iron deficiency.Every year, approximately 30% of patients suffer fromTable 2 Physical parameters of herbal granulesPhysical parameters Herbal granules prepared with10% starch solutionBulk density, g/mL 0.46 ± 0.01Tapped density, g/mL 0.48 ± 0.01Hausner quotient 1.07 ± 0.01Carr’s compressibility, % 6.72 ± 0.53Angle of repose, o 32.29 ± 0.99Flow rate, g/sec 6.67 ± 0.57*The values represent mean ± SD for three samplesTable 3 Physical parameters of herbal nutraceutical tabletsprepared with 10% starch solutionPhysical parameters ValueUniformity of weight, mg 610.5 ± 1.70Uniformity of thickness, mm 3.78 ± 0.041Hardness, kg/cm2 3.88 ± 0.078Friability, % 0.65 ± 0.020Disintegration time, s 295.33 ± 1.52*The values represent mean ± SD for three samplesTable 4 Proximate composition of herbal nutraceutical tablesProximate composition Total amount, %Moisture 62.44 ± 2.11Carbohydrates 1.88 ± 0.52Protein 0.95 ± 0.65Fat 0.43 ± 0.53Ash 1.78 ± 0.53Dietary fiber 1.66 ± 0.67Calories, kcalЦ 15.19*The values represent mean ± SD for three samplesTable 5 Minerals profile of herbal nutraceutical tabletsMinerals Total amount, mg/gIron 74.6 ± 2.7Sodium 4.4 ± 0.4Potassium 5.3 ± 0.7Calcium 163.1 ± 2.2Magnesium 39.2 ± 1.7Phosphorus 14.6 ± 2.1*The values represent mean ± SD for three samplesTable 6 Profiles of water soluble and fat-soluble vitamins inherbal nutraceutical tabletsVitamin Total amountC (ascorbic acid), mg/g 27.2 ± 4.3Vitamin B1 (thiamin), mg/g 0.6 ± 0.0Vitamin B3 (niacin), mg/g 0.6 ± 0.2Vitamin B6 (pyridoxine), mg/g 1.1 ± 0.2Vitamin B12 (cobalamin), mcg/g 0.6 ± 0.2Vitamin B9 (folic acid), mcg/g 82.6 ± 7.6Vitamin A (retinol), mcg/g 287.4 ± 6.3Vitamin D3 (cholecalciferol), mcg/g 2.6 ± 0.6Vitamin E (tocopherol), ng/g 0.7 ± 0.0*The values represent mean ± SD for three samples231Debnath B. et al. Foods and Raw Materials. 2022;10(2):227–234anemia globally, particularly 51% in India [32]. Ourherbal nutraceutical tablet had a significant amountof iron (74.6 ± 2.7 mg/g), so it may alleviate theeffects of iron deficiency (Table 5). Dietary potassiumand sodium are two electrolytes that play a vitalrole in regulating fluid and blood volume [33]. Thetablets developed contained a fair amount of sodium(4.4 ± 0.4 mg/g) and potassium (5.3 ± 0.7 mg/g),so it may be used to regulate the body’s fluidand blood volume. Calcium, phosphorus, andmagnesium are three crucial micronutrients forhealthy bone and teeth formation, as well asmetabolic functions [34]. Our herbal nutraceuticaltablets contained a considerable amount ofthese minerals, namely 163.1 ± 2.2, 14.6 ± 2.1,and 39.2 ± 1.7 mg/g, respectively. Therefore, the newlydeveloped herbal tablets can help bone formation andimprove metabolic functions in the human body.Determination of vitamins. We determined thevalues of water-soluble (C, B1, B3, B6, B12, and folicacid) and fat-soluble vitamins (A, D3, and E) in ourherbal nutraceutical tablets (Table 6). We found richamounts of vitamin C (27.2 ± 4.3 mg/g) and vitamin A(287.4 ± 6.3 mcg/g). Vitamin C is a water-solublevitamin that works as an antioxidant and improves theimmune function of the human body [35]. Vitamins B1,B3, B6, and B9 are essential for maintaining the nervoussystem, digestion, protein metabolism, red blood cells,Figure 1 Carbohydrate metabolism parameters of ob/ob mice treated with sodium carboxymethyl cellulose (normal group), sodiumcarboxymethyl cellulose (vehicle control group), metformin (positive control group), and herbal nutraceutical tablet (experimentalgroup). Each group contained six animalsc d0510152025303540-50 0 50 100 150NormalMetforminVehicleHerbal tabletBlood glucose, mMTime, minFigure 2 Change of blood glucose with time in ob/ob micetreated with sodium carboxymethyl cellulose (normal group),sodium carboxymethyl cellulose (vehicle control group),metformin (positive control group), and herbal nutraceuticaltablet (experimental group). Each group contained six animals0510152025303540-50 0 50 100 150NormalMetforminVehicleHerbal tabletBlood glucose, mMTime, min05Normal Vehicle Metformin Herbal tabletBlood 00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***0101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tablet Glycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, ##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin tabletBlood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Blood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510Normal Vehicle Metformin Herbal tabletBlood #0.51.01.52.02.53.03.54.04.5Vehicle Metformin Herbal tabletBlood changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***05Normal Vehicle Metformin Herbal tabletBlood 00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***05Vehicle Metformin Herbal tabletBlood 00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***5Vehicle Metformin Herbal tabletBlood 00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***05Vehicle Metformin Herbal tabletBlood 00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***Normal 05Normal Vehicle Metformin Herbal tabletBlood 00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet******HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0Normal Vehicle Metformin Herbal tablet00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***a b0510152025Vehicle Herbal tabletBlood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM05101520253035Normal Vehicle Metformin Herbal tabletHbAlc, ng/mL0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM##*#*0.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM##**00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM05101520253035Normal Vehicle Metformin Herbal tabletHbAlc, ng/mL0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL0510152025##*#*00.51.01.52.02.53.03.54.04.5#### ** ***05101520253035##*** ***#0510152025303540**#### ***0510Normal Vehicle Metformin Herbal tabletBlood glucose, #00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***0101520253035Normal Metformin tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Vehicle Metformin Herbal tabletBlood glucose, mM##*#*0.51.01.52.02.53.03.54.04.5Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Herbal tabletBlood glucose, ##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***051015253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Blood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***05Normal Vehicle Metformin Herbal tabletBlood 00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***5101520253035Normal Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***05Normal Vehicle Metformin Herbal tabletBlood 00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***5101520253035Normal Metformin ##*** ***HbAlc, ng/mL#05101520253035Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***05Normal Vehicle Metformin Herbal tabletBlood 00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM05101520253035Normal Metformin Herbal tabletHbAlc, ng/mL0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL05Normal Vehicle Metformin Herbal tabletBlood 00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***05Normal Vehicle Metformin Herbal tabletBlood 00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***00.51.01.52.0Normal Vehicle Metformin Herbal tabletBlood glucose during 4 weeks, ## ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Vehicle Herbal tabletGlycosylated protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Blood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***05101525Normal Metformin Herbal tabletBlood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0510152025Normal Vehicle Metformin Herbal tabletBlood glucose, mM##*#*00.51.01.52.02.53.03.54.04.5Normal Vehicle Metformin Herbal tabletBlood glucose changeduring 4 weeks, mM#### ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0.5Vehicle Metformin Herbal tabletduring 05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Herbal tabletGlycosylated serum protein,ng/mL**#### 00.51.0Normal Vehicle Herbal tabletBlood during ## ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/**#### ***00.51.0Normal Vehicle Metformin Herbal tabletBlood during ## 05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0.51.0Normal Vehicle Metformin Herbal tabletBlood during ## 05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0.51.0Normal Vehicle Metformin Herbal tabletBlood during ## 05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***0***00.51.0Vehicle Metformin Herbal tabletBlood during ## ** ***05101520253035Normal Vehicle Metformin Herbal tablet##*** ***HbAlc, ng/mL#0510152025303540Normal Vehicle Metformin Herbal tabletGlycosylated serum protein,ng/mL**#### ***Normal232Debnath B. et al. Foods and Raw Materials. 2022;10(2):227–234type 2 diabetes [39]. The oral administration of theherbal tablet to ob/ob mice significantly reduced theirblood glucose level (Fig. 2). Therefore, this tablet maybe used as an anti-diabetic drug.We also found that the herbal nutraceutical tablet(200 mg/kg) significantly enhanced oral glucosetolerance (Fig. 2). This means that this tablet can be usedto alleviate type 2 diabetes mellitus through progressinginsulin sensitivity.CONCLUSIONOur study showed that the newly formulated herbaltablet contained optimal amounts of macro- andmicronutrients, water, and fat-soluble vitamins. Thetablet also provided significantly higher hypoglycemicactivity compared to the standard drug, metformin.The results suggested that the herbal tablets developedmay be recommended as an anti-diabetic herbalremedy.CONTRIBUTIONThe authors were equally involved in writing themanuscript and are equally responsible for plagiarism.CONFLICT OF INTERESTThe authors have declared no conflict of interest inrelation to this manuscript.and skin health. Vitamins A, D3, and E are commonfat-soluble vitamins that support such body functionsas vision, hair growth, bone maintenance, immunesystem regulation, oxidative stress prevention, etc. [36].Our herbal nutraceutical tablets contained fair amountsof vitamins D3, E, and B group (Table 6). Therefore,they may be used to treat diseases caused by theirdeficiency.Anti-diabetic activity. The treatment of ob/obmice with our herbal nutraceutical tablets (200 mg/kgbody weight) significantly decreased their fasting bloodglucose, serum hemoglobin, and glycosylated serumprotein (Fig. 1). The effectiveness of the herbal tabletwas comparable to that of metformin, a standard drug(200 mg/kg body weight).A fasting blood glucose test, which is generallycalled a fasting plasma glucose test, measures theamount of glucose in the blood and determines thepatient’s risk of prediabetes or diabetes [37]. Ournewly formulated herbal tablet (200 mg/kg) reducedthe fasting blood glucose level (Fig. 1a and 1b).Serum hemoglobin and glycosylated serum proteinare important indicators for the long-term glycemiccontrol [38]. Our experiment showed that the herbaltablet (200 mg/kg) reduced their levels, compared tometformin (200 mg/kg) (Fig. 1c and 1d).An oral glucose tolerance test determines the body’sresponse to glucose. This test can be used to detect</p>
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