Physiological Effects of a Novel Immune Stimulator Drug, (1,4)‐α‐d‐Glucan, in Rats

Abstract

The (1,4)-a-D-glucan (a-D-glucan), derived from medicinal plant, Tinospora cordifolia, activates human lymphocytes with downstream synthesis of the pro-and anti-inflammatory cytokines, in vitro. We investigated physiological and immunological effects of a low and a high dose of a-D-glucan (0.5 and 10 mg/kg), in vivo, testing the hypothesis that intravenous administration of a-D-glucan does not affect haemodynamic, respiratory, haematological, and immune responses in normal rats. Male rats (300-400 g) were anaesthetized, tracheostomized, and catheterized in one femoral artery and vein. The mean arterial blood pressure and heart rate were continuously recorded. The baselines for gas exchange, differential blood cell count, and plasma concentration of TNF-a, IL-1b, IL-4, IL-6, and IFN-c were determined. Rats were then randomly assigned to controls (n ¼ 7), a low dose (0.5 mg/kg; n ¼ 10), and a high dose (10 mg/kg; n ¼ 7) of a-D-glucan for a six 6 hr study period. Gas exchange, differential cell count, plasma concentration of TNF-a, IL-1b, IL-4, IL-6, and IFN-c, and mean arterial blood pressure values remained within physiological range. Intravenous administration of 10 mg/kg a-D-glucan created tachycardia, associated with hyperventilation, and significant reductions in the blood haemoglobin and haematocrit concentrations. We suggest that these in vivo effects of a-D-glucan should be considered for future clinical and/or experimental trials.Extracts from a medicinal plant, Tinospora cordifolia, are shown to have anti-tumour activity [1,2], to reduce the pathological effects of endotoxic shock [3], and to inhibit lethal irradiation injury [4]. Studies suggest that glucans have modulating effects on inflammatory cytokines [5,6]. Extracts from other medicinal plants are known to enhance immune responses [7], and/or participate in scavenging of excessive reactive oxygen and nitrogen species [8,9]. The water-soluble polysaccharide (1,4)-a-d-glucan (a-d-glucan) is isolated from T. cordifolia and is known to activate different subsets of lymphocytes in vitro at 100 lg/ml [10]. This activation is followed by production of both pro-and antiinflammatory cytokines, such as TNF-a, IL-1b, IL-6, IL-12, IL-18, IFN-c, and MCP-1, involving Th1 pathway of T helper cell differentiation [5].The physiological effects of such immune-stimulating agents have been rarely studied. The half-life of glucans, given intravenously, is relatively short [11] and in practice multiple doses of glucans might be required to produce a maintained and significant change in inflammatory cytokine production. No study has examined the immediate effects of a single and relatively low dose of glucans, intravenously, in normal animals. In the present study, therefore, we tried to establish the physiological characteristics of a-d-glucan, to be considered for the design of future experimental and clinical trials. We tested whether intravenous administration of a-d-glucan can affect vital physiological variables, which are ordinarily used during critica...

Immunostimulatory properties of the major protein from the stem of the Ayurvedic medicinal herb, guduchi (Tinospora cordifolia)

“…An immunologically active arabinogalactan named G1-4A (M r 2.2 × 10 6 ) has been isolated, and the molecular events in the activation of B cells and macrophages by G1-4A has been demonstrated (Chintalwar et al, 1999;Desai et al, 2002;Raghu et al, 2009). Recently, a novel polysaccharide termed RR1 (␣-d-glucan) of molecular mass >550 kDa exhibiting unique immune stimulating properties has been isolated, and its physiological effects and mechanism of macrophage activation in rats have been studied in detail (Nair et al, 2004(Nair et al, , 2006Koppada et al, 2009).…”

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“…Correa ex, [18][19] Bacopa monnieri, 20 Solanum nigrum Linn., 21 Plumbago zeylanica L., [22][23][24] Coriandrum sativum Linn., 25 Leucas aspera (Willd.) Link, 26 Tinospora cordifolia (Wild) Meirs., [27][28][29][30][31][32][33][34][35][36][37][38][39][40] Terminalia chebula Retz., 41 Premna integrifolia Linn., 42 Carum carvi L., 43 Piper longum L., [44][45][46][47][48][49] Centella asiatica Linn., [50][51] Cyperus rotundus L., 52 Vitex nirgundo L., 53 Nelumbo nucifera Gaertn., [54][55] Moringa oleifera Lam., [56][57] Cedrus deodara (Roxb.) Loud., 58 Acorus calamus L., 2 Boerhavia diffusa Linn., 59 Embelia ribes Burn F., 2 Citrullus colocynthis Schrad., 60 Terminalia bellerica (Gaertn.)…”

Modulation of Inflammatory Response to Implanted Biomaterials Using Natural Compounds

“…Various active ingredients including alkaloids, steroids, diterpenoids, lactones, aliphatics, and glycosides can be extracted from different parts of this plant [149]. Published data have shown the potential of tinospora cordifolia to treat various diseases due to its anti-diabetic, anti-malarial, anti-oxidant, anti-allergic, and anti-inflammatory properties [24, 149–153]. Diterpenoids, lactones, and aliphatic compounds are responsible for the anti-inflammatory effects of this plant [149].…”

“…Diterpenoids, lactones, and aliphatic compounds are responsible for the anti-inflammatory effects of this plant [149]. Tinosfora cordifolia regulates both pro- and anti-inflammatory pathways by the activation of various cytokines [153]. In one study, Sannegowda et al .…”