Table 2.

Molecular mechanisms of various pharmacological activities of inulin.

Activity of inulin	Model system	Mechanism of action	References
Antioxidant activities	In vitro (model-free)	Compared to Vitamin C, free radical scavenging activity of inulin was weak and significantly lower as evident from DPPH radical scavenging activity, ABTS scavenging activity and ferric reducing power assays.	[43]
	In vivo (laying hens)	Inulin has shown the significant dose-dependent increase in the levels of MDA and serum antioxidant enzymes such as SOD, CAT, and GSD-Px (p < 0.001).
	Colonic smooth muscle cells	Inulin has shown a significantly higher antioxidant activity compared to simple sugars and remained unaltered regardless of cooking and digestion processes (p < 0.05).	[44]
	In vitro (model-free)	Inulin-containing hydrogels showed controllable antioxidant properties in response to the thermo-sensitive water affinity of the network with a DPPH reduction of 74 % and 55 % in swollen and shrunk states respectively.	[45]
Protection against LPS-induced oxidative stress	Human colonic smooth muscle cell	Pre-incubation of LPS with inulin has shown a significant reduction of maximal acetylcholine (Ach)-induced contraction in smooth muscle cells.	[46]
Immunomodulatory effects in intestine	Intestinal epithelial cells	Regulated the intestinal inflammation (through Treg), maintained intestinal-barrier homeostasis (by expressing tight junction proteins, sIgA and Muc2 in goblet and plasma cells), improved the intestinal barrier (by promoting IL-22 secretion by ILC3s and γδ T cells), enhanced the anti-tumor effect by regulating the epigenetics and inhibiting the tumor growth by infiltration of γδ T cells and CD8+ T cells.	[47]
Anti-obesity	Randomized, double-blinded placebo-controlled study (obese Thai children aged 7–15 years)	Obese children, when supplemented with inulin containing diet, significantly increased the fat-free mass index and decreased the fat mass index (FMI), BMI z-score, and trunk FMI.	[48]
	Randomized, single-blinded, multicentric, placebo-controlled trial was conducted in obese participants (placebo: n = 31, prebiotic: n = 30)	Obese subjects who increased physical activity along with a 3-month intervention with an inulin-enriched diet decreased BMI (−1.6kg/m2), reduced plasma cholesterol and liver enzymes, and increased glucose tolerance.	[49]
Anticancer property	Human colon cell lines (LT97 and HT29); Female BALB/c mice and male C57BL/6 mice (6–8weeks old); Male Swiss mice (6 weeks old)	Inulin stimulated apoptosis and reduced proliferation of tumor cells; stimulated memory T-cell responses, and intensified α-PD-1; significant reduction in the levels of carcinoembryonic antigen and aberrant crypt foci due to the variation of JNK-1/β-catenin signaling mechanism.	[50–52]
Anti-inflammatory activity	Male F344 rats (4–5 weeks old)	Inulin decreased azoxymethane (AOM)-induced carcinogenesis in rats.	[53]
Vaccine adjuvant and delivery system	In Vitro Dendritic Cells (DC2.4)	Soluble inulin microparticles (sIMs) took up the antigen in a higher proportion by >25 times when presented them to antigen-presenting cells (APCs) versus in solution (99 % vs. 22 %).	[54]
	Male BALB/c mice (6–8 weeks old)	sIMs produced robust Th2-type antibody titers (IgG1: 500,000) compared to unadjuvanted antigens (IgG1: 17,500) or alum-adjuvanted antigens (IgG1: 80,000).	[54]
	Randomized clinical subjects (281 adults aged 18–70 years)	11.1-fold raise in antibody titers was noted in 80 % (95 % CI: 52–96) of 18–49 years old who received recombinant hemagglutinin (rHA)-based vaccine (45 μg) with Advax™ adjuvant made of semi-crystalline delta inulin. Advax™ adjuvant increased seroprotection rates by 1.9 times and 2.5 times after the first and the second immunizations respectively, when compared to rHA alone.	[55]
Antiviral activity	Horses, including pregnant mares and foals aged 74–152 days.	Japanese encephalitis virus (JEV) vaccine (JE-ADVAX™) containing delta inulin as an adjuvant proved as a well-tolerated, effective, and safe, in inducing protective levels of JEV-neutralizing antibodies with partial cross-neutralization of Murray Valley encephalitis virus and a new variant strain of Kunjin virus, a subtype of West Nile virus.	[56]
Cartilage regeneration	Bovine chondrocytes	Bovine chondrocytes, when encapsulated during crosslinking of amino-functionalized hyaluronic acid derivatives with divinylsulfone functionalized inulin (INU-DV), sufficiently survived and efficiently proliferated until 28 days of analysis.	[57]
Prebiotic effect	Bifidobacteria and Lactobacilli	Inulin stimulates the growth of beneficial bacteria, such as Bifidobacteria and Lactobacilli, in the colon, promoting a healthy gut microbiota.	[58] [59]
Technological functionality	Model free	Inulin exhibited various technological properties, including gelation, thickening, and structure stabilization, making it widely utilized in the food industry.	[60]
Physiological functionality	Fischer 344 rats (5 weeks old)	Inulin has been shown to have physiological functionalities such as being bifidogenic, laxative, and promoting the production of beneficial short-chain fatty acids in the large intestine.	[61] [59]
Fat replacement	Raw cow’s milk (3 % fat); skim milk and Cream (40 % fat)	Inulin can be used as a fat replacer in food products, affecting properties such as moisture content, firmness, and spreadability.	[62] [63]
Blood pressure regulation	Randomized, placebo-controlled, double-blinded, parallel intervention trial (116 overweight or obese participants)	Systolic (5.35 ± 2.4 mmHg, p = 0.043) as well as diastolic (2.82 ± 1.3 mmHg, p = 0.047) blood pressure has been reduced with the fiber supplementation compared to placebo.	[64]
Antidiabetic	Randomized, triple-blind controlled trial, 49 females (fiber intake <30 g/day) with type 2 diabetes	Inulin supplementation significantly decreased fasting plasma glucose (8.47 %), glycosylated hemoglobin (10.43 %), and malondialdehyde (37.21 %) levels (p < 0.05).	[65]
	Randomized clinical trials (48 adults with prediabetes or at increased risk for T2D)	Supplementation with prebiotic inulin significantly reduced cardiometabolic risk in individuals at risk of T2D (p < 0.05).	[66]
Cardiometabolic disease	Male LDL receptor-deficient mice (7 weeks old)	Inulin-fed mice displayed a decreased C16:0/C24:0 plasma ceramide (Cer) ratio and lower levels of circulating ceramides associated with VLDL and LDL. Liver transcriptomic analysis revealed that Smpd3, a gene that encodes neutral SMase (NSMase), was downregulated by 2-fold in inulin-fed mice. Hepatic NSMase activity was 3-fold lower in inulin-fed mice than in controls. Furthermore, liver redox status and compositions of phosphatidylserine and FFA species, the major factors that determine NSMase activity, were also modified by inulin.	[67]
Anti-hypercholesterolemic effects	Randomized, double-blind, crossover trial (Men and women (n = 21)	Baseline LDL increased significantly during the control phase. There were small, nonsignificant declines in total cholesterol (1.3 %) and LDL-C (2.1 %) during the inulin phase. Differences in response between periods (inulin - control) were significant (p < 0.05) for LDL-C (−14.4 %) and total cholesterol (−8.7 %).	[68]