{"id":55613,"date":"2024-03-20T10:50:30","date_gmt":"2024-03-20T10:50:30","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=55613"},"modified":"2024-04-02T04:10:53","modified_gmt":"2024-04-02T04:10:53","slug":"influence-of-allium-sativum-on-the-hypoglycaemic-activity-of-gliclazide-in-normal-rats-a-possible-approach-to-herb-drug-interaction","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no1\/influence-of-allium-sativum-on-the-hypoglycaemic-activity-of-gliclazide-in-normal-rats-a-possible-approach-to-herb-drug-interaction\/","title":{"rendered":"Influence of Allium Sativum on the Hypoglycaemic Activity of Gliclazide in Normal Rats: A Possible Approach to Herb-Drug Interaction"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

The\nmechanisms behind the majority of reported herb-drug interactions are unclear.\nHowever, these interactions are significantly influenced by changed medication\nmetabolism, absorption, and clearance caused by combination herbs. Numerous\nherbs can change medication concentration and clearance by inducing or\ninhibiting cytochrome P450s and other liver and intestine drug metabolizing\nenzymes. According to clinical investigations, cyclosporine, digoxin,\namitriptyline, nevirapine, indinavir, theophylline, oral contraceptives, and\nsimvastatin plasma concentrations were all decreased by St. John’s wort.\nPrednisolone, a synthetic steroid utilized in a variety of compounds as an\nanti-inflammatory, anti-allergic medication and immune suppressive. Licorice\nraises the plasma concentration of prednisolone1<\/sup>.The primary cause\nof these observed herb-drug interactions is thought to be the stimulation or\ninhibition of cytochrome P450s.<\/p>\n\n\n\n

On the other hand, some components of herbs may interact with drugs in a synergistic or antagonistic manner by acting on the identical drug target molecules (such as receptors or enzymes). While antagonistic interactions can lead to decreased efficacy & therapeutic failure, combined outcomes may cause adverse effects & intricate the dose schedule of long-term medications2<\/sup>.<\/p>\n\n\n\n

So monitoring drug therapy and study of food-drug interactions has become important to get a clear data about the food-drug interactions. It is very essential to study the food-drug interactions in tracking of pharmacotherapy along with other drugs in case of some disorders like diabetes and hypertension. Since a slight decrease or increase in the plasma concentration of the drug may lead to either decrease in the effect or may lead to toxic effect. Depending upon the data obtained modification in the dosage regimen (if at all needed) is done for the better therapeutic benefit with maximal safety.<\/p>\n\n\n\n

Type-II diabetes is more\ncommon than type-I (juvenile) diabetes. Most preferable drug in the treatment\nof diabetes are sulphonylureas. Amongst them gliclazide is extensively used\nmedication because of its high potency, long duration of action, lower\nincidence of side effects and antioxidant property. In these modern days the\nconsumption of fast foods is increasing. Fast foods contain large amount of\nspices and many of these spices reported to have many biological properties. Allium sativum <\/em>(garlic) is a most\ncommonly used spices in many types of Indian, Arabic as well as in western\ndiets3<\/sup>. Garlic is reported to lower blood glucosein animal models.\nHence in the current research it is planned to find its influence on blood\nglucose in addition to gliclazide pharmacodynamic activity in normal rat models.<\/p>\n\n\n\n

Materials and Methods<\/strong><\/p>\n\n\n\n

Inbred mature\nalbino wistar rats of both the sex were purchased from Ghosh Enterprises,\nKolkata, India. The prior authorization for the study was acquired from our\nInstitutional Animal Ethics Committee (IAEC). Gliclazide (5 gm) sample was\nobtained from Wock Hardt Pharmaceuticals, Ourangabad, India. Blood glucose kits\n(Auto span) manufactured by Span diagnostics Limited, Surat, India are purchased\nfrom a local supplier. Standard animal pellet dietary supplements for animals, designed\nby Rayan Biotechnologies Private Limited, Hyderabad, India was taken. Gliclazide\nwas dissolved in a few drops of 0.1 N Sodium Hydroxide and then diluted with\ndistilled water to the desired volume. Allium sativum<\/em> aqueous suspension\nwas prepared by dissolving it in distilled water4<\/sup>. <\/p>\n\n\n\n

In\nthe study, albino wistar rats of both the sex ranging from 180-200 gm are used.\nRats were split into three groups, each group with 6 rats. Rats were kept in a\nstandard environment with a 12 hr \/12hr light and dark cycle. They were kept in\ncages made of polypropylene. Rats were given a normal animal pellet diet along\nwith water5<\/sup>.<\/p>\n\n\n\n

Prior\nto the trial, the rats were fasted for 18 hr with access to water and ad\nlibitum<\/em>. Additionally water was withdrawn during the experiment. Gliclazide\nwas administered orally at 0.5 mg\/kg, 1 mg\/kg, 2 mg\/kg body weight to group-I,\ngroup-II and group-III respectively. By retro-orbital puncture, blood samples are\nwithdrawn at 0, 1, 2, 3, 4, 6, 8, 10, 12 & 16 hr intervals to analyze blood\nglucose by GOD\/POD method6<\/sup>.<\/p>\n\n\n\n

Results<\/strong><\/p>\n\n\n\n

With gliclazide<\/strong><\/p>\n\n\n\n

A dose of 1 mg\/kg body weight of gliclazide produced hypoglycaemia with\nabout 43.78 (1 hr) and\n41.51 (12 hr) mean percent reduction in blood\nglucose.The same dose was taken for interaction study. Dose dependent response\nwas observed with the three doses tried (0.5, 1 and 2 mg\/kg). The optimal blood\nglucose reduction, which is the STD of gliclazide was chosen based on ideal\nblood glucose reduction which is about 30-40%. 0.5 mg\/kg of gliclazide (oral) produced 17.43 (1 hr) and 19.8 (4 hr)\nmean percent reduction in blood glucose and 2 mg\/kg of gliclazide produced 57.75 (2 hr) and 56.4 (10 hr) mean percent\nreduction in blood glucose.The blood glucose levels observed with 0.5 mg\/kg,\n1 mg\/kg, 2 mg\/kg rat body weight of gliclazide were\nshown in table 1, 2 and 3 respectively. The percent blood glucose reduction\nwith 0.5 mg\/kg,1 mg\/kg, 2 mg\/kg rat body weight\nof gliclazide was shown in table 1, 2 and 3 respectively and the graphical\nrepresentation was done in figure 1.<\/p>\n\n\n\n

Table 1: Blood glucose levels (mg\/dL) with gliclazide (0.5 mg\/kg body weight) in normal rats<\/strong>.<\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Time<\/strong><\/p>\n

(hr)<\/strong><\/p>\n<\/td>\n

\n

Rats<\/strong><\/p>\n<\/td>\n

\n

Mean \u00b1SEM<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

R1<\/strong><\/p>\n<\/td>\n

\n

R2<\/strong><\/p>\n<\/td>\n

\n

R3<\/strong><\/p>\n<\/td>\n

\n

R4<\/strong><\/p>\n<\/td>\n

\n

R5<\/strong><\/p>\n<\/td>\n

\n

R6<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

0<\/p>\n<\/td>\n

\n

67<\/p>\n<\/td>\n

\n

96<\/p>\n<\/td>\n

\n

109<\/p>\n<\/td>\n

\n

88<\/p>\n<\/td>\n

\n

76<\/p>\n<\/td>\n

\n

67<\/p>\n<\/td>\n

\n

83.8\u00b11.29<\/p>\n<\/td>\n<\/tr>\n

\n

1<\/p>\n<\/td>\n

\n

62<\/p>\n

(7.4)<\/p>\n<\/td>\n

\n

80<\/p>\n

(16.6)<\/p>\n<\/td>\n

\n

69<\/p>\n

(36.9)<\/p>\n<\/td>\n

\n

49<\/p>\n

(44.2)<\/p>\n<\/td>\n

\n

71<\/p>\n

(6.58)<\/p>\n<\/td>\n

\n

73<\/p>\n

(-7.0)<\/p>\n<\/td>\n

\n

70.5\u00b13.03<\/p>\n<\/td>\n<\/tr>\n

\n

2<\/p>\n<\/td>\n

\n

65<\/p>\n

(2.9)<\/p>\n<\/td>\n

\n

98<\/p>\n

(-2.1)<\/p>\n<\/td>\n

\n

93<\/p>\n

(14.86)<\/p>\n<\/td>\n

\n

56<\/p>\n

(36.36)<\/p>\n<\/td>\n

\n

72<\/p>\n

(5.45)<\/p>\n<\/td>\n

\n

41<\/p>\n

(38.0)<\/p>\n<\/td>\n

\n

70.8\u00b13.45<\/p>\n<\/td>\n<\/tr>\n

\n

3<\/p>\n<\/td>\n

\n

50<\/p>\n

(25.37)<\/p>\n<\/td>\n

\n

69<\/p>\n

(28.12)<\/p>\n<\/td>\n

\n

103<\/p>\n

(5.4)<\/p>\n<\/td>\n

\n

48<\/p>\n

(45.45)<\/p>\n<\/td>\n

\n

72<\/p>\n

(5.26)<\/p>\n<\/td>\n

\n

74<\/p>\n

(-10.4)<\/p>\n<\/td>\n

\n

69.6\u00b12.49<\/p>\n<\/td>\n<\/tr>\n

\n

4<\/p>\n<\/td>\n

\n

45<\/p>\n

(32.4)<\/p>\n<\/td>\n

\n

90<\/p>\n

(6.24)<\/p>\n<\/td>\n

\n

65<\/p>\n

(40.6)<\/p>\n<\/td>\n

\n

79<\/p>\n

(10.23)<\/p>\n<\/td>\n

\n

79<\/p>\n

(-3.4)<\/p>\n<\/td>\n

\n

47<\/p>\n

(29.8)<\/p>\n<\/td>\n

\n

67.5\u00b11.05<\/p>\n<\/td>\n<\/tr>\n

\n

6<\/p>\n<\/td>\n

\n

53<\/p>\n

(20.89)<\/p>\n<\/td>\n

\n

95<\/p>\n

(1.04)<\/p>\n<\/td>\n

\n

126<\/p>\n

(-15.6)<\/p>\n<\/td>\n

\n

91<\/p>\n

(-4.5)<\/p>\n<\/td>\n

\n

55<\/p>\n

(27.63)<\/p>\n<\/td>\n

\n

47<\/p>\n

(29.8)<\/p>\n<\/td>\n

\n

77.8\u00b11.32<\/p>\n<\/td>\n<\/tr>\n

\n

8<\/p>\n<\/td>\n

\n

70<\/p>\n

(-4.7)<\/p>\n<\/td>\n

\n

80<\/p>\n

(-1.04)<\/p>\n<\/td>\n

\n

79<\/p>\n

(27.5)<\/p>\n<\/td>\n

\n

79<\/p>\n

(-3.4)<\/p>\n<\/td>\n

\n

74<\/p>\n

(2.6)<\/p>\n<\/td>\n

\n

76<\/p>\n

(14.9)<\/p>\n<\/td>\n

\n

77.6\u00b11.71<\/p>\n<\/td>\n<\/tr>\n

\n

10<\/p>\n<\/td>\n

\n

59<\/p>\n

(19.4)<\/p>\n<\/td>\n

\n

97<\/p>\n

(1.04)<\/p>\n<\/td>\n

\n

134<\/p>\n

(-22.4)<\/p>\n<\/td>\n

\n

87<\/p>\n

(1.36)<\/p>\n<\/td>\n

\n

78<\/p>\n

(-2.6)<\/p>\n<\/td>\n

\n

57<\/p>\n

(3.0)<\/p>\n<\/td>\n

\n

88.16\u00b11.75<\/p>\n<\/td>\n<\/tr>\n

\n

12<\/p>\n<\/td>\n

\n

74<\/p>\n

(-10.4)<\/p>\n<\/td>\n

\n

89<\/p>\n

(7.7)<\/p>\n<\/td>\n

\n

131<\/p>\n

(-20)<\/p>\n<\/td>\n

\n

74<\/p>\n

(15.4)<\/p>\n<\/td>\n

\n

67<\/p>\n

(11.8)<\/p>\n<\/td>\n

\n

65<\/p>\n

(16.83)<\/p>\n<\/td>\n

\n

85.3\u00b12.22<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Table 2: Blood glucose levels (mg\/dL) with gliclazide (1 mg\/kg body weight) in normal rats<\/strong>.<\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Time<\/strong><\/p>\n

(hr)<\/strong><\/p>\n<\/td>\n

\n

Rats<\/strong><\/p>\n<\/td>\n

\n

Mean \u00b1SEM<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

R1<\/strong><\/p>\n<\/td>\n

\n

R2<\/strong><\/p>\n<\/td>\n

\n

R3<\/strong><\/p>\n<\/td>\n

\n

R4<\/strong><\/p>\n<\/td>\n

\n

R5<\/strong><\/p>\n<\/td>\n

\n

R6<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

0<\/p>\n<\/td>\n

\n

101<\/p>\n<\/td>\n

\n

89<\/p>\n<\/td>\n

\n

83<\/p>\n<\/td>\n

\n

103<\/p>\n<\/td>\n

\n

112<\/p>\n<\/td>\n

\n

115<\/p>\n<\/td>\n

\n

100.5\u00b12.8916<\/p>\n<\/td>\n<\/tr>\n

\n

1<\/p>\n<\/td>\n

\n

64<\/p>\n

(36.63)<\/p>\n<\/td>\n

\n

54<\/p>\n

(39.33)<\/p>\n<\/td>\n

\n

44<\/p>\n

(46.99)<\/p>\n<\/td>\n

\n

58<\/p>\n

(43.69)<\/p>\n<\/td>\n

\n

57<\/p>\n

(49.11)<\/p>\n<\/td>\n

\n

61<\/p>\n

(46.96)<\/p>\n<\/td>\n

\n

56.3\u00b13.8044<\/p>\n<\/td>\n<\/tr>\n

\n

2<\/p>\n<\/td>\n

\n

57<\/p>\n

(43.56)<\/p>\n<\/td>\n

\n

50<\/p>\n

(43.82)<\/p>\n<\/td>\n

\n

66<\/p>\n

(20.48)<\/p>\n<\/td>\n

\n

70<\/p>\n

(32.04)<\/p>\n<\/td>\n

\n

90<\/p>\n

(19.64)<\/p>\n<\/td>\n

\n

59<\/p>\n

(48.69)<\/p>\n<\/td>\n

\n

65.3\u00b13.7193<\/p>\n<\/td>\n<\/tr>\n

\n

3<\/p>\n<\/td>\n

\n

48<\/p>\n

(52.47)<\/p>\n<\/td>\n

\n

62<\/p>\n

(30.34)<\/p>\n<\/td>\n

\n

51<\/p>\n

(38.55)<\/p>\n<\/td>\n

\n

59<\/p>\n

(42.72)<\/p>\n<\/td>\n

\n

80<\/p>\n

(28.57)<\/p>\n<\/td>\n

\n

71<\/p>\n

(38.37)<\/p>\n<\/td>\n

\n

61.83\u00b13.6395<\/p>\n<\/td>\n<\/tr>\n

\n

4<\/p>\n<\/td>\n

\n

54<\/p>\n

(46.53)<\/p>\n<\/td>\n

\n

52<\/p>\n

(41.57)<\/p>\n<\/td>\n

\n

45<\/p>\n

(45.78)<\/p>\n<\/td>\n

\n

73<\/p>\n

(29.13)<\/p>\n<\/td>\n

\n

62<\/p>\n

(44.64)<\/p>\n<\/td>\n

\n

86<\/p>\n

(25.72)<\/p>\n<\/td>\n

\n

62\u00b15.2915<\/p>\n<\/td>\n<\/tr>\n

\n

6<\/p>\n<\/td>\n

\n

81<\/p>\n

(19.8)<\/p>\n<\/td>\n

\n

40<\/p>\n

(55.1)<\/p>\n<\/td>\n

\n

40<\/p>\n

(51.81)<\/p>\n<\/td>\n

\n

82<\/p>\n

(20.38)<\/p>\n<\/td>\n

\n

104<\/p>\n

(7.14)<\/p>\n<\/td>\n

\n

86<\/p>\n

(25.22)<\/p>\n<\/td>\n

\n

72.16\u00b14.1081<\/p>\n<\/td>\n<\/tr>\n

\n

8<\/p>\n<\/td>\n

\n

88<\/p>\n

(12.87)<\/p>\n<\/td>\n

\n

50<\/p>\n

(43.82)<\/p>\n<\/td>\n

\n

55<\/p>\n

(33.73)<\/p>\n<\/td>\n

\n

55<\/p>\n

(46.6)<\/p>\n<\/td>\n

\n

64<\/p>\n

(42.86)<\/p>\n<\/td>\n

\n

77<\/p>\n

(33.04)<\/p>\n<\/td>\n

\n

64.83\u00b12.2535<\/p>\n<\/td>\n<\/tr>\n

\n

10<\/p>\n<\/td>\n

\n

93<\/p>\n

(7.92)<\/p>\n<\/td>\n

\n

50<\/p>\n

(43.82)<\/p>\n<\/td>\n

\n

67<\/p>\n

(19.27)<\/p>\n<\/td>\n

\n

56<\/p>\n

(45.63)<\/p>\n<\/td>\n

\n

66<\/p>\n

(41.06)<\/p>\n<\/td>\n

\n

76<\/p>\n

(33.91)<\/p>\n<\/td>\n

\n

68\u00b12.8156<\/p>\n<\/td>\n<\/tr>\n

\n

12<\/p>\n<\/td>\n

\n

91<\/p>\n

(9.9)<\/p>\n<\/td>\n

\n

52<\/p>\n

(41.57)<\/p>\n<\/td>\n

\n

58<\/p>\n

(30.12)<\/p>\n<\/td>\n

\n

43<\/p>\n

(58.25)<\/p>\n<\/td>\n

\n

52<\/p>\n

(53.57)<\/p>\n<\/td>\n

\n

51<\/p>\n

(55.65)<\/p>\n<\/td>\n

\n

57.83\u00b13.0048<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Table 3: Blood glucose levels (mg\/dL) with gliclazide (2 mg\/kg body weight) in normal rats<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Time<\/strong><\/p>\n

(hr)<\/strong><\/p>\n<\/td>\n

\n

Rats<\/strong><\/p>\n<\/td>\n

\n

Mean \u00b1SEM<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

R1<\/strong><\/p>\n<\/td>\n

\n

R2<\/strong><\/p>\n<\/td>\n

\n

R3<\/strong><\/p>\n<\/td>\n

\n

R4<\/strong><\/p>\n<\/td>\n

\n

R5<\/strong><\/p>\n<\/td>\n

\n

R6<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

0<\/p>\n<\/td>\n

\n

103<\/p>\n<\/td>\n

\n

114<\/p>\n<\/td>\n

\n

76<\/p>\n<\/td>\n

\n

104<\/p>\n<\/td>\n

\n

107<\/p>\n<\/td>\n

\n

78<\/p>\n<\/td>\n

\n

97\u00b11.16<\/p>\n<\/td>\n<\/tr>\n

\n

1<\/p>\n<\/td>\n

\n

27<\/p>\n

(73.77)<\/p>\n<\/td>\n

\n

35<\/p>\n

(69.29)<\/p>\n<\/td>\n

\n

32<\/p>\n

(57.89)<\/p>\n<\/td>\n

\n

47<\/p>\n

(71.1)<\/p>\n<\/td>\n

\n

30<\/p>\n

(54.81)<\/p>\n<\/td>\n

\n

82<\/p>\n

(-5.13)<\/p>\n<\/td>\n

\n

42.17\u00b12.43<\/p>\n<\/td>\n<\/tr>\n

\n

2<\/p>\n<\/td>\n

\n

21<\/p>\n

(79.61)<\/p>\n<\/td>\n

\n

25<\/p>\n

(78.67)<\/p>\n<\/td>\n

\n

24<\/p>\n

(68.42)<\/p>\n<\/td>\n

\n

28<\/p>\n

(69.16)<\/p>\n<\/td>\n

\n

33<\/p>\n

(73.67)<\/p>\n<\/td>\n

\n

95<\/p>\n

(-21.79)<\/p>\n<\/td>\n

\n

37.67\u00b12.42<\/p>\n<\/td>\n<\/tr>\n

\n

3<\/p>\n<\/td>\n

\n

40<\/p>\n

(61.16)<\/p>\n<\/td>\n

\n

63<\/p>\n

(44.74)<\/p>\n<\/td>\n

\n

61<\/p>\n

(19.74)<\/p>\n<\/td>\n

\n

39<\/p>\n

(44.86)<\/p>\n<\/td>\n

\n

59<\/p>\n

(62.7)<\/p>\n<\/td>\n

\n

111<\/p>\n

(-42.31)<\/p>\n<\/td>\n

\n

62.17\u00b12.89<\/p>\n<\/td>\n<\/tr>\n

\n

4<\/p>\n<\/td>\n

\n

44<\/p>\n

(57.28)<\/p>\n<\/td>\n

\n

76<\/p>\n

(33.33)<\/p>\n<\/td>\n

\n

31<\/p>\n

(59.21)<\/p>\n<\/td>\n

\n

27<\/p>\n

(42.05)<\/p>\n<\/td>\n

\n

62<\/p>\n

(74.04)<\/p>\n<\/td>\n

\n

104<\/p>\n

(-33.33)<\/p>\n<\/td>\n

\n

57.33\u00b12.02<\/p>\n<\/td>\n<\/tr>\n

\n

6<\/p>\n<\/td>\n

\n

42<\/p>\n

(59.22)<\/p>\n<\/td>\n

\n

40<\/p>\n

(64.91)<\/p>\n<\/td>\n

\n

29<\/p>\n

(61.84)<\/p>\n<\/td>\n

\n

28<\/p>\n

(83.24)<\/p>\n<\/td>\n

\n

18<\/p>\n

(73.07)<\/p>\n<\/td>\n

\n

100<\/p>\n

(-28.2)<\/p>\n<\/td>\n

\n

42.83\u00b12.62<\/p>\n<\/td>\n<\/tr>\n

\n

8<\/p>\n<\/td>\n

\n

38<\/p>\n

(63.11)<\/p>\n<\/td>\n

\n

40<\/p>\n

(64.91)<\/p>\n<\/td>\n

\n

24<\/p>\n

(68.42)<\/p>\n<\/td>\n

\n

22<\/p>\n

(82.2)<\/p>\n<\/td>\n

\n

19<\/p>\n

(78.85)<\/p>\n<\/td>\n

\n

104<\/p>\n

(-33.3)<\/p>\n<\/td>\n

\n

41.17\u00b11.37<\/p>\n<\/td>\n<\/tr>\n

\n

10<\/p>\n<\/td>\n

\n

40<\/p>\n

(61.16)<\/p>\n<\/td>\n

\n

31<\/p>\n

(72.18)<\/p>\n<\/td>\n

\n

33<\/p>\n

(56.58)<\/p>\n<\/td>\n

\n

23<\/p>\n

(73.83)<\/p>\n<\/td>\n

\n

28<\/p>\n

(77.88)<\/p>\n<\/td>\n

\n

81<\/p>\n

(-3.84)<\/p>\n<\/td>\n

\n

39.33\u00b14.39<\/p>\n<\/td>\n<\/tr>\n

\n

12<\/p>\n<\/td>\n

\n

46<\/p>\n

(55.34)<\/p>\n<\/td>\n

\n

41<\/p>\n

(64.03)<\/p>\n<\/td>\n

\n

26<\/p>\n

(65.79)<\/p>\n<\/td>\n

\n

30<\/p>\n

(71.96)<\/p>\n<\/td>\n

\n

30<\/p>\n

(71.15)<\/p>\n<\/td>\n

\n

112<\/p>\n

(-43.58)<\/p>\n<\/td>\n

\n

47.5\u00b13.57<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n\n
\"\"<\/td>\n\n

Figure 1: Percent reduction of blood glucose with different doses of gliclazide in normal rats (n=6).<\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

With Allium sativum<\/em>  <\/strong><\/p>\n\n\n\n

Allium\nsativum <\/em>has shown effect on the blood glucose\nlevels when administered alone. The blood glucose levels observed with 1 mg\/kg\nof gliclazide prior to and following treatment of Allium sativum<\/em> (104\nmg\/kg) were shown in table 2 and 5 respectively. The mean percent blood glucose\nreductions observed with 1 mg\/kg of gliclazide before and after Allium\nsativum <\/em>(104 mg\/kg) treatment were shown in table 2 and 5 respectively and\ngraphically represented in figure 2. <\/p>\n\n\n\n

The\nblood glucose levels and percent blood glucose reduction with Allium sativum\n<\/em>(104 mg\/kg) were shown in table 4. <\/p>\n\n\n\n

The\ncombination of Allium sativum <\/em>(104 mg\/kg) and gliclazide (1 mg\/kg)\nproduced a mean percent blood glucose reduction\n53.8 (2 hr) and 41.3 (8\nhr) (table 5), while gliclazide matching control produced 43.78 (1 hr) and 35.48 (8 hr)\n(table 2). <\/p>\n\n\n\n

The\nstudent\u2019s paired t-test was applied to the data to find out the statistical\nsignificance between combination (Allium sativum <\/em>+ gliclazide) group and\ngliclazide matching control group. The enhancement of gliclazide induced\nhypoglycaemic effect by Allium sativum <\/em>was statistically significant at\ntime intervals of the study i.e. at 2nd <\/sup>hr intervals.<\/p>\n\n\n\n

Table 4: Blood glucose levels (mg\/dL) with Allium sativum<\/em> (104 mg\/kg body weight) in normal rats<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Time (hr)<\/strong><\/p>\n<\/td>\n

\n

Rats<\/strong><\/p>\n<\/td>\n

\n

Mean \u00b1SEM<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

R1<\/strong><\/p>\n<\/td>\n

\n

R2<\/strong><\/p>\n<\/td>\n

\n

R3<\/strong><\/p>\n<\/td>\n

\n

R4<\/strong><\/p>\n<\/td>\n

\n

R5<\/strong><\/p>\n<\/td>\n

\n

R6<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

0<\/p>\n<\/td>\n

\n

75<\/p>\n<\/td>\n

\n

110<\/p>\n<\/td>\n

\n

74<\/p>\n<\/td>\n

\n

69<\/p>\n<\/td>\n

\n

62<\/p>\n<\/td>\n

\n

70<\/p>\n<\/td>\n

\n

76.6\u00b16.9<\/p>\n<\/td>\n<\/tr>\n

\n

1<\/p>\n<\/td>\n

\n

80<\/p>\n

(-6.6)<\/p>\n<\/td>\n

\n

76<\/p>\n

(-8.8)<\/p>\n<\/td>\n

\n

87<\/p>\n

(-17.56)<\/p>\n<\/td>\n

\n

67<\/p>\n

(2.9)<\/p>\n<\/td>\n

\n

72<\/p>\n

(-16.9)<\/p>\n<\/td>\n

\n

75<\/p>\n

(-7.1)<\/p>\n<\/td>\n

\n

76.2\u00b12.7<\/p>\n<\/td>\n<\/tr>\n

\n

4<\/p>\n<\/td>\n

\n

82<\/p>\n

(-9.3)<\/p>\n<\/td>\n

\n

79<\/p>\n

(55.4)<\/p>\n<\/td>\n

\n

91<\/p>\n

(-22.9)<\/p>\n<\/td>\n

\n

71<\/p>\n

(-2.89)<\/p>\n<\/td>\n

\n

76<\/p>\n

(-22.6)<\/p>\n<\/td>\n

\n

74<\/p>\n

(-5.7)<\/p>\n<\/td>\n

\n

79\u00b12.8<\/p>\n<\/td>\n<\/tr>\n

\n

8<\/p>\n<\/td>\n

\n

56<\/p>\n

(25.3)<\/p>\n<\/td>\n

\n

52<\/p>\n

(52.72)<\/p>\n<\/td>\n

\n

72<\/p>\n

(2.7)<\/p>\n<\/td>\n

\n

59<\/p>\n

(14.49)<\/p>\n<\/td>\n

\n

44<\/p>\n

(29.0)<\/p>\n<\/td>\n

\n

60<\/p>\n

(14.3)<\/p>\n<\/td>\n

\n

57.1\u00b13.7<\/p>\n<\/td>\n<\/tr>\n

\n

10<\/p>\n<\/td>\n

\n

57<\/p>\n

(24.0)<\/p>\n<\/td>\n

\n

58<\/p>\n

(47.27)<\/p>\n<\/td>\n

\n

80<\/p>\n

(-8.1)<\/p>\n<\/td>\n

\n

71<\/p>\n

(-2.89)<\/p>\n<\/td>\n

\n

38<\/p>\n

(38.7)<\/p>\n<\/td>\n

\n

79<\/p>\n

(-12.8)<\/p>\n<\/td>\n

\n

63.8\u00b16.5<\/p>\n<\/td>\n<\/tr>\n

\n

12<\/p>\n<\/td>\n

\n

50<\/p>\n

(33.3)<\/p>\n<\/td>\n

\n

48<\/p>\n

(56.36)<\/p>\n<\/td>\n

\n

81<\/p>\n

(-9.4)<\/p>\n<\/td>\n

\n

57<\/p>\n

(25.0)<\/p>\n<\/td>\n

\n

45<\/p>\n

(27.41)<\/p>\n<\/td>\n

\n

58<\/p>\n

(17.1)<\/p>\n<\/td>\n

\n

56.4\u00b15.3<\/p>\n<\/td>\n<\/tr>\n

\n

16<\/p>\n<\/td>\n

\n

41<\/p>\n

(45.3)<\/p>\n<\/td>\n

\n

48<\/p>\n

(56.36)<\/p>\n<\/td>\n

\n

67<\/p>\n

(9.45)<\/p>\n<\/td>\n

\n

58<\/p>\n

(22.4)<\/p>\n<\/td>\n

\n

72<\/p>\n

(-16.12)<\/p>\n<\/td>\n

\n

58<\/p>\n

(17.1)<\/p>\n<\/td>\n

\n

57.2\u00b14.7<\/p>\n<\/td>\n<\/tr>\n

\n

20<\/p>\n<\/td>\n

\n

55<\/p>\n

(26.6)<\/p>\n<\/td>\n

\n

47<\/p>\n

(56.0)<\/p>\n<\/td>\n

\n

69<\/p>\n

(6.75)<\/p>\n<\/td>\n

\n

58<\/p>\n

(7.2)<\/p>\n<\/td>\n

\n

72<\/p>\n

(2.67)<\/p>\n<\/td>\n

\n

58<\/p>\n

(37.0)<\/p>\n<\/td>\n

\n

55.8\u00b13.7<\/p>\n<\/td>\n<\/tr>\n

\n

24<\/p>\n<\/td>\n

\n

62<\/p>\n

(17.3)<\/p>\n<\/td>\n

\n

55<\/p>\n

(50.0)<\/p>\n<\/td>\n

\n

71<\/p>\n

(4.05)<\/p>\n<\/td>\n

\n

64<\/p>\n

(7.2)<\/p>\n<\/td>\n

\n

62<\/p>\n

(0.00)<\/p>\n<\/td>\n

\n

55<\/p>\n

(21.4)<\/p>\n<\/td>\n

\n

61.5\u00b14.6<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Table 5: Blood glucose levels (mg\/dL) with gliclazide (1mg\/kg body weight) in combination with Allium sativum<\/em> (104 mg\/kg body weight) in normal rats<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Time<\/strong><\/p>\n

(hr)<\/strong><\/p>\n<\/td>\n

\n

Rats<\/strong><\/p>\n<\/td>\n

\n

Mean \u00b1SEM<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

R1<\/strong><\/p>\n<\/td>\n

\n

R2<\/strong><\/p>\n<\/td>\n

\n

R3<\/strong><\/p>\n<\/td>\n

\n

R4<\/strong><\/p>\n<\/td>\n

\n

R5<\/strong><\/p>\n<\/td>\n

\n

R6<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

0<\/p>\n<\/td>\n

\n

70<\/p>\n<\/td>\n

\n

59<\/p>\n<\/td>\n

\n

71<\/p>\n<\/td>\n

\n

65<\/p>\n<\/td>\n

\n

67<\/p>\n<\/td>\n

\n

66<\/p>\n<\/td>\n

\n

66.4 \u00b1 1.7<\/p>\n<\/td>\n<\/tr>\n

\n

1<\/p>\n<\/td>\n

\n

55<\/p>\n

(21.4)<\/p>\n<\/td>\n

\n

28<\/p>\n

(52.5)<\/p>\n<\/td>\n

\n

45<\/p>\n

(35.7)<\/p>\n<\/td>\n

\n

37<\/p>\n

(43.1)<\/p>\n<\/td>\n

\n

67<\/p>\n

(0.00)<\/p>\n<\/td>\n

\n

37<\/p>\n

(43.9)<\/p>\n<\/td>\n

\n

44 \u00b1 5.7<\/p>\n<\/td>\n<\/tr>\n

\n

2<\/p>\n<\/td>\n

\n

35<\/p>\n

(50.0)<\/p>\n<\/td>\n

\n

30<\/p>\n

(53.8)<\/p>\n<\/td>\n

\n

44<\/p>\n

(38.0)<\/p>\n<\/td>\n

\n

42<\/p>\n

(35.4)<\/p>\n<\/td>\n

\n

34<\/p>\n

(49.3)<\/p>\n<\/td>\n

\n

29<\/p>\n

(56.1)<\/p>\n<\/td>\n

\n

30.7 \u00b1 2.5<\/p>\n<\/td>\n<\/tr>\n

\n

3<\/p>\n<\/td>\n

\n

53<\/p>\n

(24.2)<\/p>\n<\/td>\n

\n

38<\/p>\n

(35.6)<\/p>\n<\/td>\n

\n

52<\/p>\n

(26.8)<\/p>\n<\/td>\n

\n

60<\/p>\n

(7.7)<\/p>\n<\/td>\n

\n

42<\/p>\n

(37.3)<\/p>\n<\/td>\n

\n

52<\/p>\n

(21.2)<\/p>\n<\/td>\n

\n

49.5 \u00b1 3.3<\/p>\n<\/td>\n<\/tr>\n

\n

4<\/p>\n<\/td>\n

\n

56<\/p>\n

(-20.0)<\/p>\n<\/td>\n

\n

24<\/p>\n

(59.3)<\/p>\n<\/td>\n

\n

54<\/p>\n

(23.9)<\/p>\n<\/td>\n

\n

43<\/p>\n

(36.1)<\/p>\n<\/td>\n

\n

40<\/p>\n

(40.3)<\/p>\n<\/td>\n

\n

38<\/p>\n

(42.4)<\/p>\n<\/td>\n

\n

42.4 \u00b1 4.7<\/p>\n<\/td>\n<\/tr>\n

\n

6<\/p>\n<\/td>\n

\n

40<\/p>\n

(42.8)<\/p>\n<\/td>\n

\n

33<\/p>\n

(44.1)<\/p>\n<\/td>\n

\n

47<\/p>\n

(33.8)<\/p>\n<\/td>\n

\n

45<\/p>\n

(30.1)<\/p>\n<\/td>\n

\n

40<\/p>\n

(40.3)<\/p>\n<\/td>\n

\n

37<\/p>\n

(37.9)<\/p>\n<\/td>\n

\n

41 \u00b1 2.1<\/p>\n<\/td>\n<\/tr>\n

\n

8<\/p>\n<\/td>\n

\n

37<\/p>\n

(47.1)<\/p>\n<\/td>\n

\n

29<\/p>\n

(50.8)<\/p>\n<\/td>\n

\n

48<\/p>\n

(32.3)<\/p>\n<\/td>\n

\n

47<\/p>\n

(27.7)<\/p>\n<\/td>\n

\n

36<\/p>\n

(46.3)<\/p>\n<\/td>\n

\n

37<\/p>\n

(43.9)<\/p>\n<\/td>\n

\n

39 \u00b1 3<\/p>\n<\/td>\n<\/tr>\n

\n

10<\/p>\n<\/td>\n

\n

49<\/p>\n

(30.0)<\/p>\n<\/td>\n

\n

41<\/p>\n

(30.5)<\/p>\n<\/td>\n

\n

61<\/p>\n

(14.1)<\/p>\n<\/td>\n

\n

49<\/p>\n

(24.6)<\/p>\n<\/td>\n

\n

37<\/p>\n

(44.8)<\/p>\n<\/td>\n

\n

42<\/p>\n

(36.4)<\/p>\n<\/td>\n

\n

46.5 \u00b1 3.5<\/p>\n<\/td>\n<\/tr>\n

\n

12<\/p>\n<\/td>\n

\n

48<\/p>\n

(-31.4)<\/p>\n<\/td>\n

\n

40<\/p>\n

(32.2)<\/p>\n<\/td>\n

\n

51<\/p>\n

(28.2)<\/p>\n<\/td>\n

\n

44<\/p>\n

(32.3)<\/p>\n<\/td>\n

\n

36<\/p>\n

(46.3)<\/p>\n<\/td>\n

\n

39<\/p>\n

(40.1)<\/p>\n<\/td>\n

\n

43 \u00b1 2.4<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

*Significant at P < 0.05 compared to gliclazide (1mg\/kg) matching control.<\/p>\n\n\n\n
\"\"<\/td>\n\n

Figure 2: Percent reduction of blood glucose of Gliclazide, Allium sativum<\/em> and combination of Gliclazide and Allium sativum<\/em><\/strong><\/p>\n

<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Discussion<\/strong><\/p>\n\n\n\n

A biphasic blood glucose level drop was caused by\ngliclazide. It is known that sulphonylureas stimulate insulin secretion and\nimprove glucose uptake at cellular level. It is well established that insulin cause\nsecretion and improve tissue utilization of glucose at cellular levels7-9<\/sup>.\nThe biphasic effect might be due to its secretion and reabsorption through bile\ninto the duodenum by Entero-hepatic cycling as reported earlier. Allium sativum<\/em>  alone produced a slight reduction in blood\nglucose level, this could be because of the presence of S-allyl cysteine and\nother proposed mechanism of actions was insulin secretagogue through pancreatic\nsecretion\/release of bound insulin10-12<\/sup>.<\/p>\n\n\n\n

The acute dose of Allium sativum <\/em>when administered in combination with\ngliclazide  enhanced the hypoglycemic\nactivity of gliclazide at 2nd<\/sup>, 6th<\/sup> and 8th <\/sup>hr\nintervals but it was significant at 2nd<\/sup> hr only and the effect was\nshown to be reduced at all other ie.,1st<\/sup>, 3rd<\/sup>,10th<\/sup>\nand 12th<\/sup> hr time intervals. This shows that the aqueous extract of Allium sativum <\/em>is influencing the\nabsorption pattern of gliclazide since it was reported to have an increasing\nmotility of the gastro intestinal tract13-14<\/sup>.<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

The dose related hypoglycaemic effect was\nobserved for 0.5 mg\/kg, 1 mg\/kg, 2 mg\/kg rat body weight of gliclazide with in\nnormal rats. Allium sativum<\/em> alter the blood glucose level, but when\ngiven in combination with gliclazide, enhanced the hypoglycaemic impact of\ngliclazide in normal rats demonstrating the existence of interaction.<\/p>\n\n\n\n

Acknowledgement<\/strong><\/p>\n\n\n\n

Authors are thankful to V. V. Institute of Pharmaceutical Sciences, Gudlavalleru, India for providing necessary facilities of research work.<\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

There is no conflict of interest.<\/p>\n\n\n\n

Funding Sources<\/strong><\/p>\n\n\n\n

There are no funding sources.<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

  1. Eswar Kumar K, Ramesh A, Yadav RS, Satyanarayana S. Determination of gliclazide in rabbit serum by RP-HPLC. Acta Ciencia Indica. Chemistry. <\/em>2007;33(3):273-278.<\/li>
  2. Trinder P. Determination of blood glucose using an oxidaseperoxidase system with a non-carcinogenic chromogen. Journal of Clinical Pathology. <\/em>1969;22(2):158-161.
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  3. Beatrice I. Research article:Effects of Garlic on Cytochromes P450 2C9and 3A4-Mediated Drug Metabolism in Human Hepatocytes.Sceintia<\/em>. 2010;78:473-481.
    CrossRef <\/a><\/li>
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    CrossRef <\/a><\/li>
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     CrossRef <\/a><\/li>
  7. Mathew PT, Augusti KT. Studies on the effect of allicin (diallyl disulphide-oxide) on alloxan diabetes I. Hypoglycaemic action and enhancement of serum insulin effect and glycogen synthesis. Indian J BiochemBiophys. <\/em>1973;10:209-212.<\/li>
  8. Sheela CG, Augusti KT. Antidiabetic effects of S-allyl cysteine sulphoxide isolated from garlic Allium Sativum Linn. Indian J Exp Biol. <\/em>1992;30:523-526.<\/li>
  9. H. Miyazaki T, FujiiK, Yoshida S. Arakawa, Furukawa H. Disposition and metabolism of [3H] gliclazide in rats. European Journal of Drug Metabolism and Pharmacokinetics. <\/em>1983;2(4):117-131.
     CrossRef <\/a><\/li>
  10. Cerveny JC, Leder ,Weart CW. Issues surrounding tight glycemic control in people with type 2 diabetes mellitus. Ann Pharmacother<\/em>. 1998;32(9):869-905.
     CrossRef <\/a><\/li>
  11. Fetrow CW, Avila JR. Professionsals Handbook of Complementary and Alternative Medicine. Springhouse Corporation.<\/em>1999.<\/li>
  12. Gribble FM, Tucker SJ, Seino S, Ashcroft FM. Tissuue specificity of sulfonylureas: studies on cloned cardiac and beta-cell K(ATP) channels. Diabetes. <\/em>1998;47(9):1412-1418.
    CrossRef <\/a><\/li>
  13. Schernthaner G. Gliclazide modified release: A critical review of pharmacodynamic, metabolic and vasoprotective effects. Metabolism. <\/em>2003;52(8):29-34.
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  14. Zeigler O, Drouin P. Hemobiological properties of gliclazide. J diabetes complications. <\/em>1994;8(4):235-239.
    CrossRef <\/a><\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

    Introduction The mechanisms behind the majority of reported herb-drug interactions […]<\/p>\n","protected":false},"author":15,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[113],"tags":[],"class_list":["post-55613","post","type-post","status-publish","format-standard","hentry","category-vol17no1"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/55613","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=55613"}],"version-history":[{"count":5,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/55613\/revisions"}],"predecessor-version":[{"id":57465,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/55613\/revisions\/57465"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=55613"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=55613"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=55613"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}