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Endotoxin & Liver | Bioactives Research

In product development we were drawn to the liver because it is a primary site for lipopolysaccharide (LPS) clearance. To create a product to optimise liver function, was therefore high on our priority list. Over the next couple of weeks we will share some of the research behind the bioactives for liver and LPS clearance.

In product development we were drawn to the liver because it is a primary site for lipopolysaccharide (LPS) clearance. To create a product to optimise liver function, was therefore high on our priority list. Over the next couple of weeks we will share some of the research behind the bioactives for liver and LPS clearance.

Selenium

Selenium is an important micronutrient that is incorporated into selenoproteins, which have a wide range of pleiotropic effects, including antioxidant and anti-inflammatory, as well as involvement in thyroid metabolism. Selenium is an important co-factor of the antioxidant enzyme systems that protect the liver from reactive oxygen species (ROS), and support phase 1 and 2 detoxification pathways (1).

Selenium supports our endogenous antioxidant systems that are involved in protection from LPS-induced ROS.

 

Hibiscus

Hibiscus sabdariffahas traditionally been used in India and Africa as a food and medicinal plant (2, 3). One of its traditional uses is as an antidote to food or chemical poisoning (2). Hibiscus contains many phytochemicals, such as the flavanols delphinidin and cyanidin, hibiscitrin, gossypitrin and sabdaritrin, protocatechuic acid and arabinogalactans (3).

Protocatechuic acid has been shown to inhibit LPS-induced hepatic damage in rats and reduce liver enzymes and inflammatory cytokines in an LPS model (4, 5). The polyphenols in hibiscus have been shown to have strong antioxidant and anti-inflammatory properties (4, 6) and their pleiotropic effects may be useful in obesity-associated metabolic syndrome largely via the antioxidant-protective effects on the liver, as well as promoting lipid clearance (7); see figure 1.

A drink given to elderly subjects ameliorated LPS-induced renal inflammation via downregulation of the pro-inflammatory cytokine network, and the NF-κB pathway. The drink also reduced the incidence of UTIs in residents with urinary catheters by 36% in long-term care facilities (8).

Hibiscus has antioxidant, anti-inflammatory, hepatoprotective and LPS-clearing abilities.

 

hibiscus antioxidant
Figure 1: Multiple effects of Hibiscus polyphenols on intracellular redox homeostasis. The antioxidant abilities of HS polyphenols (HSp), represented by colored hexagons, act directly or indirectly upon intracellular ROS generation in oxidative status. HSp antioxidant activity blocks intracellular ROS generation in hydrophilic environments and also the generation of lipoperoxy radicals, which are major responsible for DNA oxidative damage. Alternatively, HSp may act indirectly by up-regulating antioxidant enzymes expression or protein activation (7).

 

Burdock Root

Arctium lappa is a large perennial herb that is traditionally used in Western, Native American and Chinese medicine. It is one of the constituents in the popular Essiac™ Tea, which is a popular formula used in people with cancer (9). In folk medicine, burdock roots were popular remedies for hypertension, gout, hepatitis and other inflammatory disorders (10).

Burdock root has been shown to possess hepatoprotective (11), anti-inflammatory  (12) and free radical scavenging activities in pharmacological and research trials (10, 13). These activities are attributed to the presence of caffeoylquinic acid derivatives, whilst the chemo-preventative effects are associated to lignans such as arctiin and arctigenin (14).

In a human clinical trial, patients saw a significant decrease in IL-6, hsCRP and malondialdehyde (a marker of oxidative stress), while levels of serum total antioxidant capacity and activities of superoxide dismutase (SOD) were significantly increased, in comparison to controls, after three cups of burdock tea daily (15). In a similar study, cholesterol and lipoprotein levels improved, and blood pressure reduced (16).

In an inflammatory model of LPS-induced endotoxin shock, arctigenin was shown to ameliorate inflammation by regulating myeloid-derived suppressor cells (MDSCs), which are potent T cell suppressors (17). Arctigenin also shows anti-inflammatory and antioxidative effects on LPS-induced acute lung injuries (18).

Burdock has hepatoprotective and antioxidant, and LPS-induced inflammation modulating capacities.

References
  1. Rayman MP. Selenium and human health. Lancet [Internet]. 2012;379(9822):1256–68. Available from: http://dx.doi.org/10.1016/ S0140-6736(11)61452-9
  2. Abat JK, Kumar S, Mohanty A. Ethnomedicinal, Phytochemical and Ethnopharmacological Aspects of Four Medicinal Plants of Malvaceae Used in Indian Traditional Medicines: A Review. Medicines. 2017;4(4):75.
  3. Badreldin HA, Naser Al W, Gerald B. Phytochemical, pharmacological and toxicological aspects of Hibiscus sabdariffa L.: a review. Phyther Res [Internet]. 2005;19(5):369–75. Available from: http://dx.doi.org/10.1002/ptr.1628
  4. KAO E-S, HSU J-D, WANG C-J, YANG S-H, CHENG S-Y, LEE H-J. Polyphenols Extracted from Hibiscus sabdariffa L. Inhibited Lipopolysaccharide-Induced Inflammation by Improving Antioxidative Conditions and Regulating Cyclooxygenase -2 Expression . Biosci Biotechnol Biochem. 2009;73(2):385–90.
  5. WL L, Hsieh Y, Chou F, Wang C, Cheng M, Tseng T. Hibiscus protocatechuic acid inhibits lipopolysaccharide-induced rat hepatic damage. Arch Toxicol. 2003;77(1):42–7.
  6. Zhen J, Villani TS, Guo Y, Qi Y, Chin K, Pan MH, et al. Phytochemistry, antioxidant capacity, total phenolic content and anti-inflammatory activity of Hibiscus sabdariffa leaves. Food Chem [Internet]. 2016;190:673–80. Available from: http://dx.doi. org/10.1016/j.foodchem.2015.06.006
  7. Herranz-López M, Olivares-Vicente M, Encinar JA, Barrajón-Catalán E, Segura-Carretero A, Joven J, et al. Multi-targeted molecular effects of Hibiscus sabdariffa polyphenols: An opportunity for a global approach to obesity. Nutrients. 2017;9(8).
  8. Chou ST, Lo HY, Li CC, Cheng LC, Chou PC, Lee YC, et al. Exploring the effect and mechanism of Hibiscus sabdariffa on urinary tract infection and experimental renal inflammation. J Ethnopharmacol. 2016;194(October):617–25.
  9. Tamayo C, Richardson MA, Diamond S, Skoda I. The chemistry and biological activity of herbs used in FloraEssenceTM herbal tonic and Essiac. Phyther Res. 2002;14(1):1–14.
  10. Predes FS, Ruiz ALTG, Carvalho JE, Foglio MA, Dolder H. Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts. BMC Complement Altern Med. 2011;11:1–5.
  11. El-Kott AF, Bin-Meferij MM. Use of Arctium lappa Extract Against Acetaminophen-Induced Hepatotoxicity in Rats. Curr Ther Res - Clin Exp [Internet]. 2015;77:73–8. Available from: http://dx.doi.org/10.1016/j.curtheres.2015.05.001
  12. Conea S, Mogosan C, Vostinaru O, Toma CC, Cuc Hepcal I, Cazacu I, et al. Polyphenolic Profile, Anti-Inflammatory and Antinociceptive Activity of an Extract from Arctium lappa L. Roots. Not Bot Horti Agrobot Cluj-Napoca. 2017;45(1):59.
  13. Duh P. Antioxidant Activity of Burdock (Arctium lappa Linné): Its Scavenging Effect on Free-Radical and Active Oxygen. JAOCS. 1998;75(4):455–61.
  14. Ferracane R, Graziani G, Gallo M, Fogliano V, Ritieni A. Metabolic profile of the bioactive compounds of burdock (Arctium lappa) seeds, roots and leaves. J Pharm Biomed Anal. 2010;51(2):399–404.
  15. Abed R, Alipoor B, Maghsoumi-Norouzabad L, Mesgari-Abbasi M, Asghari Jafarabadi M, Eftekhar Sadat B. Effects of Arctium lappa L. (Burdock) root tea on inflammatory status and oxidative stress in patients with knee osteoarthritis . Int J Rheum Dis. 2014;255–61.
  16. Maghsoumi-Norouzabad L, Shishehbor F, Abed R, Zare Javid A, Eftekhar-Sadat B, Alipour B. Effect of Arctium lappa linne (Burdock) Root tea consumption on lipid profile and blood pressure in patients with knee osteoarthritis. J Herb Med [Internet]. 2019;100266. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2210803319300120
  17. Shi H, Dong G, Yan F, Zhang H, Li C, Ma Q, et al. Arctigenin Ameliorates Inflammation by Regulating Accumulation and Functional Activity of MDSCs in Endotoxin Shock. Inflammation. 2018;41(6):2090–100.
  18. Zhang W zhou, Jiang Z kui, He B xia, Liu X ben. Arctigenin Protects against Lipopolysaccharide-Induced Pulmonary Oxidative Stress and Inflammation in a Mouse Model via Suppression of MAPK, HO-1, and iNOS Signaling. Inflammation. 2015;38(4):1406–14.

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