Research Highlights

Pharmacology

  1. Antioxidant Activity
  2. Anti-inflammatory Activity


  1. Antioxidant Activity
  2. Recently, attention has been focused on Tetrahydrocurcuminoids, because this compound appears to exert a greater antioxidant activity than Curcumin in both in vitro and in vivo systems5,3 .Okada et al3 (2001) have claimed that THC has more potent antioxidant activity than Curcumin.


    3.Okada et al(2001) Curcumin and especially Tetrahydrocurcumin ameliorate oxidative stress induced renal injury in mice. J Nutr. 21, 2090-2095.


    5. Pari L. and Murugan P. (2004). Protective role of tetrahydrocurcumin against erythromycin estolate induced hepatotoxicity. Pharmacol Res 49, 481-486.

    (a) Comparative Antioxidant activity of Tetrahydrocurcuminoids with other curcuminoids.

    In a series of studies conducted by Sabinsa Corporation6, the free radical scavenging ability of Curcumin (C), BDMC and THC were evaluated by using DPPH (1.1 diphenyl-2-picrylhydrazyl)-radical scavenging method. The results shown in Fig. 2 indicate that all test compounds resulted in significant neutralization of free radicals in a dose-dependent manner, with THC being the most effective, followed by Curcumin and BDMC.

    Free radical scavenging ability of THC in comparison with Curcumin and BDMC

    Fig 2. Free radical scavenging ability of THC in comparison with Curcumin and BDMC


    Ref 5. Majeed et al 1995. Curcuminoids: antioxidant phytonutrients. Sabinsa Corporation NJ. USA

    (b) Inhibition of AAPH induced Linoleic Acid Oxidation by Curcuminoids

    AAPH (2,2′-azobis(2-amidinopropane) dihydrochloride) is a water-soluble azo compound which is used extensively in the studies on lipid peroxidation as a free radical generator.

    A comparative study to identify anti-oxidant activity of Curcumin, its natural Demethoxy derivatives [Demethoxy curcumin and Bis demethoxy curcumin] and metabolite hydrogenated derivatives including Tetrahydrocurcuminoids, was carried out, AAPH induced linoleic oxidation and AAPH induced red blood cell hemolysis assays.

    In the AAPH induced linoleic oxidation model, it was found by the researchers that hydrogenated derivatives of Curcuminoids ie. Tetrahydrocurcuminoids, hexahydrocurcuminoids, octahydrocurcuminoids were stronger than the non hydrogenated curcuminoids- Curcumin, demethoxy curcumin, bisdemethoxy curcumin (Fig 3).

    There was a significant decrease in hemolysis of red blood cells induced by the inhibition of AAPH in the order OHC > THC = HHC > TROLOX > Curcumin = DMC. The Demethoxy derivatives of Curcumin showed lower antioxidant activity in all experimental models, thus suggesting the involvement of the ortho-methoxyphenolic groups in antioxidant activity. On the other hand, hydrogenation at conjugated double bonds of the central seven carbon chain and β - diketone of Curcumin to THC, HHC and OHC remarkably enhanced antioxidant activity (Fig 4).

    Lipid peroxidation inhibition by Curcuminoids, their hydrogenated derivatives and Trolox.

    Fig. 3 : Lipid peroxidation inhibition by Curcuminoids, their hydrogenated derivatives and Trolox.

    Lipid peroxidation inhibition by Curcuminoids, their hydrogenated derivatives and Trolox.

    Fig. 4: Comparison of Time to 50% of Maximal Hemolysis (HT50) of Curcumin, Its Derivatives and Trolox at 30µM.


    Ref 6. Somparn P. et al (2007). Comparative antioxidant activities of Curcumin and its demethoxy and hydrogenated derivatives. Biol Pharm. Bull. 30(1) 74-78.

    The studies done to understand the mechanism of action, showed that the benzylic hydrogens and not the beta –diketone moiety of Tetrahydrocurcuminoids are responsible for the enhanced antioxidant activity of THC over that of curcumin (Fig. 5)7.

    5

    Fig 5.

    Ref 7: Elise Portes et al. (2007). A comparative study on the antioxidant properties of Tetrahydrocurcuminoids and curcuminoids. Tetrahedron. 63, 9092-9099.



  3. Anti-inflammatory Activity
  4. Tetrahydrocurcuminoids show a potent anti-inflammatory activity similar to its natural parent compound- curcumin. In one of the studies, curcuminoids, sodium curcuminate and Tetrahydrocurcumin were evaluated for their anti-inflammatory activity in carrageenan-induced paw edema model in rats. The results show that Tetrahydrocurcumin was effective at almost half the dose of curcumin itself. The anti-inflammatory potency of the curcumin, Tetrahydrocurcumin, sodium curcuminate and phenylbutazone were found to be in following order (Fig 6)5

    Sodium curcuminate (NAC)>Tetrahydrocurcumin (THC) > Curcumin > Phenylbutazone (PB)

     Effect of Curcumin derivatives and phenylbutazone on carrageenan-induced paw edema in rats

    Fig 6. : Effect of Curcumin derivatives and phenylbutazone on carrageenan-induced paw edema in rats

    In a study on neuroinflammation in (chronic as well as acute) animal models using Curcumin C3 Reduct® from Sabinsa Corporation, Begum et al 8reported for the first time that Tetrahydrocurcuminoids showed efficacy in CNS oxidative damage. They showed that Tetrahydrocurcuminoids inhibited the brain inflammatory marker IL-1β better than Curcumin (1.286 µM vs 1.722 µM) in the acute inflammation model. Similar efficacy was found in chronic model also. Tetrahydrocurcuminoids were more effective than Curcumin in lowering the brain lipid peroxidation products namely F2 isoprostanes with EC50 value of 0.501 µM compared to Curcumin's 1.067 µM.


    Ref 8. Begum NA et al (2008). Curcumin structure-fubnction, bioavailability and efficacy in models of neuroinflammation and alzheimer’s disease. J Pharamcol Exp Ther. 326(1). 196-208.

  5. Anti glycation Activity
  6. Glycation is a non enzymatic chemical process in which sugar molecule chemically bonds with human DNA, lipids and proteins damaging them and leading to ultimately leading to the formation of highly reactive Advanced Glycation End products (AGEs). Glycation has been implicated in many age-related chronic diseases such as cardiovascular diseases, diabetes, cancer, alzheimer's disease, peripheral neuropathy, deafness etc. In Skin, Glycation reactions are responsible for weakening collagen fiber’s regenerative ability, which leads to the characteristics which we commonly associate with visible skin aging: wrinkling, sagging and looseness.

    An anti-glycation agent such as Tetrahydrocurcuminoids, can inhibit the glycation process and prevent the formation of AGEs (e.g. free radicals, α-dicarbonyl species, protein cross-links etc).

    THC's administered in rats with Streptozotocin-nicotinamide induced diabetes led to reduction in advanced glycation and cross linking of collagen (Table 3). The antiglycation activity of THC's was suggested to be due to their antiperoxidative activity9.

    Effect of THC’s on Hydroxyproline, Total collagen, Extent of Glycation and Levels of Fluorescence Measured in Tail Tendon in Normal and experimental Rats.

    Values are given as mean ± SD from six rats in each group; AU- Arbitrary Units; THC's- Tetrahydrocurcuminoids

    Table 6: Effect of THC’s on Hydroxyproline, Total collagen, Extent of Glycation and Levels of Fluorescence Measured in Tail Tendon in Normal and experimental Rats.

    Ref: 9 Pari L, and MuruganP. (2007). Influence of Tetrahydrocurcumin on tail tendon collagen contents and its properties in rats with streptozotocin-nicotinamide induced type 2 diabetes. Fundam Clin Pharmacol. 21(6). 665-671.

  7. Cardio Protective Potential:
  8. Cardiovascular disease though has diverse causes such as atherosclerosis, hypertension, high blood pressure, but they are leading cause of death worldwide. Atherosclerosis is characterized by thickening of artery wall due to accumulation of fatty substances such as cholesterol. The condition involves chronic inflammatory response in the walls of arteries as a result of accumulation of macrophage white blood cells promoted by low-density lipoproteins (LDL). It is also known as arteriosclerotic vascular disease (ASVD) and is commonly referred as hardening or furring of the arteries.

    Studies carried out with Tetrahydrocurcuminoids show its potential as a cardiovascular support. In a study on rabbits, it was found that Tetrahydrocurcumin was able to reduce the atherosclerotic lesions area.10

    In another study, Ischemia-reperfusion (I/R) model of myocardial infarction (MI) in male rats were taken to evaluate the cardioprotective effect of THC and Rutin. MI/R resulted in significant cardiac necrosis, elevation in lipid peroxidation, elevation in cardiac marker enzymes AST, ALT and decline in antioxidant status catalase, reduced glutathione in the normal control MI/R group and vehicle control MI/R group. MI/R caused myocardial infarction was significantly reduced by THC and Rutin causing infarct (necrosis) size reduction when compared to control group. Also, MI/R induced lipid peroxidation was significantly inhibited by THC and Rutin. Thus suppression of oxidative stress by THC and Rutin was the possible mode of cardioprotection which was confirmed by histopathological examination11.

    In another in vitro study, several anti-oxidants were compared for their efficacy to prevent the formation of trans-isomers of arachidonic acid (isomerism induced by thiyl radicals); thiyl radicals were generated by UV irradiation of 2-mercaptoethanol to induce cis-trans isomerization of Arachidonic acid.

    It was found that THC, Curcumin and Resveratrol topped the list as preventive agents (Table 4)12.

    Inhibitory effects of Antioxidants on Thiyl Radical-Induced TAA (trans arachidonic acid) formation

    Table 4: Inhibitory effects of Antioxidants on Thiyl Radical-Induced TAA (trans arachidonic acid) formation


    Ref 10: Michitaka Naito et al(2002). The protective effects of Tetrahydrocurcumin on oxidative stress in cholesterol fed rabbits. J Atheroscler Thromb. 9(5), 243- 250.


    Ref 11: Ali MS et al (2009). Cardioprotective effect of Tetrahydrocurcumin and rutin on lipid peroxides and antioxidantrs in experimentally induced myocardial infarction in rats. Pharmazie. 64(2), 132-6


    Ref 12: Wei-Lun Hung et al (2011). Inhibitory activity of natural occurring antrioxidants on thiyl radical induced trans arachidonic acid formation. J Agric Food Chem 59, 1968-1973.

  9. Renal Protection Potential:
  10. Curcumin the parent compound of Tetrahydrocurcumin is also a strong renal protective compound and much of its activity is related to reducing the inflammation in the renal tissue. Tetrahydrocurcumin has also shown potential as a renal protective agent; studies have shown this activity partly arising from its antioxidative activity. Tetrahydrocurcumin ameliorate the oxidative stress induced renal injury in mice26

    Its renal protective effect was studied on male ddY mice along with curcuminFe-NTA (ferric nitrilotriacetate) was used to induce oxidative renal injury in the experimental animals before treatment with samples. Fe-NTA is shown to increase the amount of free radical associated modified molecules as assessed by lipid peroxidation products, aldehyde modified proteins and variety of modified DNA bases such as 8-hydroxy-2'-deoxyguanosine (8-OHdG) as early as 3hrs of treatment with Fe-NTA. Therefore, oxidative suppression in the kidney was monitored by the formation of thiobarbituric acid like reactive substance (TBARS), 4-hydroxy-2-nonenal (HNE)-modified proteins, 8-OHdG etc.

    THC significantly suppressed the increase in lipid peroxidation and oxidative modification induced by Fe-NTA more effectively than curcumin. THC showed strong inhibitory effect against TBARS, HNE protein and 8-OHdG levels, suppression of the activity of glutathione peroxidase and Phase II detoxification enzymes such as NADPH: quinone reductase (NADPH:QR) and GST3


    Ref3: K Okada, C Wangpoengtrakul, T Tanaka, S Toyokuni, K Uchida, T Osawa. Curcumin and especially tetrahydrocurcumin ameliorate oxidative stress-induced renal injury in mice. J. of Nutr. 2001; 31: 2090-95

  11. Hepatoprotective Potential:
  12. Liver is a vital organ which aids in digestion, removal of toxic and waste products from the body etcDamage to liver leads to conditions such as Jaundice, Hepatitis, Cirrhosis, Haemochromatosis, Wilson’s disease, Non-alcoholic fatty liver disease, Cancer etc. Several mechanisms are responsible for either inducing hepatic injury or worsening the damage process. These include chemicals or drugs, oxidative stress, viral infections, excessive consumption of alcohol, accumulation of bile acid, over activation of cells such as hepatocytes, Kupfer cells, fat storing stellate cells and leukocytes present in the liver etc.

    Changes in biochemical markers such as Alanine transferase, Alkaline phosphatase, Bilirubin, Aspartate transaminase, Albumin, Gamma glutamyl transpeptidase, extracellular matrix proteins (collagen), Transforming growth factor (TGF)-β1 etc are often used to indicate liver damage.

    THC's and Curcumin increased the antioxidant defense through free radical scavenging in Chloroquine (CQ) induced toxicity. As THC's are more rapidly metabolized during intestinal absorption than Curcumin, they show better effect in Chloroquine induced lipid peroxidation. Thus in comparison to Curcumin, THC's show prominent effect in attenuation of Chloroquine induced lipid peroxidation13.

    In the study, female Wistar rats were administered Chloroquine (CQ) and THC’s for 8 days orally before single administration of CQ and treatment with THC’s followed for 7 more days. THC’s, showed a significant decrease in the activities of AST, ALP, ALT, levels of bilirubin and lipid peroxidation products, increase in the activity of non-enzymatic antioxidants such as plasma and liver vitamin C and vitamin E, glutathione, increase in the enzymatic antioxidants such as superoxide dismutase, catalase and glutathione peroxidase as compared to Chloroquine treated control rats. Histopathologic studies (Fig. 7 - 12) revealed near normal appearance of the liver which otherwise showed feathery degeneration and microvesicular type of fatty regeneration, sinusoidal dilation and focal necrosis in Chloroquine treated rats. The hepatoprotective potential of THC’s was found more pronounced than Curcumin13.

    Inhibitory effects of Antioxidants on Thiyl Radical-Induced TAA (trans arachidonic acid) formation

    Pathological changes of the liver such as inflammatory infiltration filling over the sinusoidal vacuolation of hepatocytic nuclei and portal triad with mild inflammation and cell infiltration were reduced in rats treated with THC's13.

    Ref 13: Pari L et al (2005). Protective role of Tetrahydrocurcumin (THC) an active principle of turmeric on chloroquine induced hepatotoxicity in rats. J Pharm Pharmaceut Sci. 8(1): 115-123.

  13. Anti-Hpyerlipidemic Activity:
  14. Hyperlipidemia is a condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood. It may be due to genetic causes such as a mutation in a receptor protein (primary hyperlipidemia) or due to other underlying causes such as diabetes (secondary hyperlipidemia). Based on the type of lipids, it can also be classified into Hypercholesterolemia, Triglyceridemia etc.

    Like the parent compounds Curcuminoids, Tetrahydorcurcuminoids were shown to have antihyperlipidemic effects in experimental diabetic rats. Administration of Tetrahydrocurcuminoids reduced the levels of serum total lipids, LDL cholesterol, VLDL cholesterol and at same time increased the levels of HDL also known as good Cholesterol. The administration of THC also reversed the changes such as increased levels of serum total lipids (Fig. 13), LDL (Low density lipids) (Fig. 14), VLDL (Very low density lipids) (Fig. 15) and also also increased levels of HDL (High density lipids) (Fig. 16) in diabetic rats. The levels of HMG CoA reductase (Fig. 17), cholesterol, triglycerides, free fatty acids and phospholipids (Fig. 18 & 19) in THC’s treated animals significantly decreased to normal levels14.


    14. Ref: Pari L. and Murugan P. (2007). Antihyperlipidemic effect of Curcumin and Tetrahydrocurcumin in Experimental Type 2 Diabetic rats. Renal failure. 29, 881-889.

    Influence of THC’s and Curcumin on serum cholesterol, triglycerides, free fatty acids and phospholipids in control and experimental rats.

    Fig. 13: Influence of THC’s and Curcumin on serum cholesterol, triglycerides, free fatty acids and phospholipids in control and experimental rats.

    Influence of THC’s and Curcumin on the levels of LDL cholesterol in control and experimental rats.

    Fig. 14: Influence of THC’s and Curcumin on the levels of LDL cholesterol in control and experimental rats.

    Influence of THC’s and Curcumin on the levels of VLDL cholesterol in control and experimental rats.

    Fig. 15: Influence of THC’s and Curcumin on the levels of VLDL cholesterol in control and experimental rats.

    Influence of THC’s and Curcumin on HDL cholesterol levels of control and experimental rats.

    Fig. 16: Influence of THC’s and Curcumin on HDL cholesterol levels of control and experimental rats.

    Influence of THC’s and Curcumin on hepatic HMG COA reductase levels of control and experimental rats.

    Fig. 17: Influence of THC’s and Curcumin on hepatic HMG COA reductase levels of control and experimental rats.

    Influence of THC’s and Curcumin on liver cholesterol, free fatty acids and triglycerides levels of control and experimental rats.

    Fig. 18: Influence of THC’s and Curcumin on liver cholesterol, free fatty acids and triglycerides levels of control and experimental rats.

     Influence of THC’s and Curcumin on liver phospholipids levels of control and experimental rats.

    Fig. 19: Influence of THC’s and Curcumin on liver phospholipids levels of control and experimental rats.

  15. Anti-cancer Potential:
  16. Cancer is characterized by uncontrolled growth of cells that invade and destroy adjacent tissues or spread to other locations in the body via lymph or blood. Cancer cells have the ability to penetrate and infiltrate surrounding normal tissues through metastasis, which is a complex cascade of events involving migration of cancer cells from the original site to other parts of the body usually lungs, liver, brain and bones through bloodstream or lymphatic system. It is reported that one of the critical steps necessary for cancer metastasis is tumor angiogenesis. Angiogenesis is a natural physiological process of growth of new capillary blood vessels from pre-existing vessels. Tumors secrete various growth factors such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) etc for inducing blood vessel growth (angiogenesis). It is reported that cancerous cells stop producing the anti-VEGF enzyme protein kinase G (PKG) that apparently limits beta-catenin (a cancer promoting gene) in normal cells which solicits angiogenesis15


    15. http://www.eurekalert.org/pub_releases/2007-07/mcog-eeb071807.php - Enzyme eliminated by cancer cells holds promise for cancer treatment.

    Since angiogenesis is also required for the spread of a tumor or metastasis, anti-angiogenic therapy is one of the most promising strategies for cancer treatment.

    Like its parent compound, THC have shown to produce both anti-proliferation and anti-angiogenesis effect16. More importantly THC showed higher potent anti-angiogenesis effect than Curcumin, which may be due toits higher anti-oxidant activity than Curcumin.

    16. Yoysungnoen P. et al. (2008). Anti-cancer and anti-angiogenic effects of Curcumin and Tetrahydrocurcumin on implanted hepatocellular carcinoma in nude mice. World J Gastroenterol. 14(13), 2003-2009.

    THC was found to express its anti-angiogenic potential without any cytotoxic activities to HepG2 cells even at the highest doses. It is suggested that anti-angiogenic properties of Curcumin and THC represent a common potential mechanism for their anti-cancer actions16.

    In a study on the development of preneoplastic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine in colons of mice, it was found that THC’s were more active than Curcumin in the inhibition of ACF development and cell proliferation17. In a subsequent study undertaken by Sabinsa in co-operation with Rutgers, State University of New Jersey. THC’s were found to be more effective than Curcumin in preventing azoxymethane-induced colon carcinogenesis. The results pointed out to the disruption of intercellular communication of crypt cells by THC’s by reducing the protein level of connexin-43, an important molecule of gap junction18.

    All these evidences strengthen the promising role of THC’s in the management of cancer.


    17. Kim J. M. et al. (1998). Chemopreventive effects of caratenoids and Curcumins on mouse colon carcinogenesis after 1,2-dimethylhydrazine initiation. Carcinogenesis. 19(1), 81-85. 18. Unpublished Results from Rutgers, The State University of New Jersey and Sabinsa Corporation.

  17. Anti-diabetic Potential:
  18. Diabetes is a group of metabolic diseases characterized by high blood sugar either because of the inability of the body to produce enough insulin or the inability to utilize the insulin so produced.

    In Type 1 diabetes, body fails to produce insulin and requires injected insulin, while in Type 2 diabetes, which is the most common type of diabetes, cells fail to use insulin properly (insulin resistance) which may be combined with an absolute insulin deficiency.

    Other forms of diabetes include congenital diabetes caused due to genetic defects of insulin secretion, cystic fibrosis-related diabetes, gestational diabetes, steroid diabetes induced by high doses of glucocorticoids etc.

    Insulin binding to receptors is the first event signifying the action of insulin. Both insulin secretion and insulin action are impaired in diabetes19 and because of the defect in insulin production or inaction, levels of glucose in the blood raises steadily leading to a condition called hyperglycemia. Persistent hyperglycemia is known to increase production of free radicals especially reactive oxygen species (ROS) from glucose auto-oxidation and protein glycosylation20.


    19. Stumvoll M. et al. (2001). Clinical features of insulin resistance and beta cell dysfunction and the relationship to type 2 diabetes. Clin Lab Med. 21(1), 31-51.


    20. Robertson R.P. et al. (2004). Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes, J. Biol. Chem. 279(41), 42351-42354

    Increase in the production of ROS causes an imbalance between ROS and cellular defense mechanisms resulting in cell dysfunction and destruction thereby injuring tissues. Increase in the level of ROS could be due to their increased production and/ or decreased destruction by nonenzymic and enzymic catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) antioxidants. Thus, the level of these antioxidant enzymes critically influences the susceptibility of various tissues to oxidative stress and is associated with the development of complications in diabetes. Also this is particularly relevant and dangerous for the beta islet, which is among those tissues that have the lowest levels of intrinsic antioxidant defenses 21-22.


    21. Lenzen S. et al. (1996). Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radic. Biol. Med. 20(3), 463-466.


    22. West I.C. et al. (2000). Radicals and oxidative stress in diabetes. Diabetic Med. 17, 171-180.

    THC's have been reported to stimulate pancreatic beta cells which play an important role in the production and secretion of insulin. Administration of THC’s to diabetic animals normalizes blood glucose and causes a marked improvement of altered carbohydrate metabolic enzymes. Studies on the effect of THC’s on the key hepatic metabolic enzymes involved in carbohydrate metabolism in streptozotocin-induced diabetic rats showed marked improvement in the activities of hexokinase, glucose-6-phosphate dehydrogenase (G6PD), glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and sorbitol dehydrogenase in liver23.

    THC's have the ability to trigger proinsulin synthesis and also insulin release which might be helpful to reduce plasma glucose and increase insulin during diabetes. Administration of THC's is shown to reduce TBARS and hydroperoxides in liver and kidney significantly (Table 8), scavenging of free radicals by increasing the activity of SOD and CAT, increasing the activities of GPx, GST, Vitamins C and E24.

    Table 5: Influence of THC's and Curcumin on the content of TBARS and Hydroperoxides in rats liver and kidney.

    Influence of THC’s and Curcumin on the content of TBARS and Hydroperoxides in rats liver and kidney.

    Streptozotocin (STZ) – nicotinamide caused significant reduction in the number of receptors on erythrocytes and insulin target tissues. It is reported that treatment with THC’s showed significant anti-hyperglycaemic activity. Moreover, this indirectly indicates that part of the anti-hyperglycaemic activity of THC’s is due to the release of insulin from the existing cells of the pancreas. THC’s have been shown to potentiate insulin secretion, causing a significant decrease in blood glucose. Apart from potentiating insulin secretion the number of insulin binding site was increased by THC’s administration in comparison to STZ–nicotinamide24.


    23 Pari L. et al. (2005). Effect of Tetrahydrocurcumin on blood glucose, plasma insulin and hepatic key enzymes in streptozotocin induced diabetic rats. J Basic Clin Physiol Pharmacol. 16(4), 257-74.


    24. Murugan P. et al. (2006). Antioxidant effect of Tetrahydrocurcumin in streptozotocin-nicotinamide induced diabetic rats. Life Sci. 79(18), 1720-1728.

    To better understand how THC's produce an antihyperglycaemic effect, the effect of THC’s on the insulin-binding sites of erythrocytes in diabetic rats was analyzed. Using circulating erythrocytes as the cellular mode, the insulin-binding effect of THC’s and Curcumin was investigated in Streptozotocin (STZ)–nicotinamide-induced experimental model in male rats. THC’s (80 mg/kg body weight) were administered orally for 45 days. The effect on blood glucose (Fig.21), plasma insulin (Fig. 22) and insulin binding to its receptor on the cell membrane of erythrocytes were studied.

    Effect of THC’s on the levels of Blood Glucose in normal and experimental rats.

    Fig. 21: Effect of THC's on the levels of Blood Glucose in normal and experimental rats.

    Effect of THC’s on the levels of Serum insulin in normal and experimental rats.

    Fig. 22: Effect of THC's on the levels of Serum insulin in normal and experimental rats.

    Administration of THC to rats at an oral dose of 80 mg/kg body weight for nearly 15 days reduced hepatotoxicity induced by the commonly used antibiotic erythromycin estolate and the anti-malarial drug chloroquine. At the same dose for nearly 45 days, THC showed an antihyperlipidemic effect in streptozotocin-nicotinamide-induced oxidative stress in diabetic rats. The membrane-bound antioxidant enzymes, which were decreased in these animals, increased significantly on THC treatment. Oral administration of THC also prevented changes in the levels of fatty acids, glucose, and insulin in the blood of diabetic rats. These studies reported that THC significantly decreased lipid peroxidation in different tissues of these rats. All these studies confirmed that THC, when compared with similar treatment doses of Curcumin, has much greater antidiabetic effects25.


    25. Anand P. et al. (2008). Biological activities of Curcumin and its analogues (Congeners) made by man and Mother Nature. Biochemical Pharmacology. 76, 1590 -1611.

  19. Anti-Alzheimer Potential:
  20. Amyloid plaques, neurofibrillary tangles and neuro-inflammation are the hallmarks of Alzheimer's disease. Several mediators in the inflammation cascade contribute both to neurodegeneration and to the production and accumulation of the β-amyloid peptide, including Interleukin IL-1β, reactive oxygen species, inducible nitric oxide synthase and lipid peroxidation products26. Considerable attention has been directed towards identifying compounds with neuroprotective properties.


    26. Akiyama H. et al. (2000). Inflammation and Alzheimer's disease. Neurobiol Aging. 21(3), 383-421.

    THC caused inhibition of iNOS protein mRNA and IL-1β in LPS induced inflammation in brain tissue of treated mice and the EC50 values were highly significant. Soluble amyloid-β seems to closely correlate with synaptic loss and neurodegenration in alzheimers27 and THC reduced it by 75%42.


    27. Frautschy SA et al. (2001) Phenolic anti-inflammatory antioxidant reversal of Aβ-induced cognitive deficits and neuropathology. Neurobiol Aging. 22(6), 993-1005

    Recent studies reveal the benefits of THC in protecting neurons against amyloid-β-induced toxicity.

    The author reported that THC reduces amyloid-β-induced

    • (i) increase in the level of reactive oxygen species,
    • (ii) decrease in mitochondrial membrane potential, and
    • (iii) caspase activation.

    Thus authors concluded that the THC confers protection against amyloid-β-induced toxicity and the antioxidant activity may contribute to its protective effect69.

  21. Anti-ageing Potential:
  22. All studies to date point towards the potential anti-aging benefits of THC’s, both in nutritional and topical use. Significantly, THC was found to have potential benefits in improving the life span of animal models. In preliminary studies, mice that started receiving diets containing THC (0.2%) at the age of 13 months had significantly longer average life spans (days, mean +/- SD) than control mice28.


    28. Kitani K. et al. (2007). The effects of tetrahydrocurcumin and green tea polyphenol on the survival of male C57BL/6 mice. Biogerontology. 8(5), 567-73.

    A recently published study (XX) showed that Tetrahydrocurcuminoids may regulate the aging process via a pathway that includes FOXO and SIR2. FOXO is a O type forkhead transcription factor which is involved in process such as aging, oxidative response etc. The study also showed that THC was able to increase the life span of Drosophila melanogaster by attenuating the oxidative stress response and aging process via FOXO29.

    29. Lan Xiang et al. Tetrahydrocurcumin extends life span and inhibits the oxidative stress response by regulating the FOXO forkhead transcription factor. Aging (2011). 3(11); 1098-1109.

    It is evident from the rapidly evolving research, that safe and versatile THC’s support healthy aging and longevity. As natural metabolites of the Curcuminoids, Tetrahydrocurcuminoids, presents an attractive option to supplement manufacturers seeking to revitalize their anti-aging formulations.