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Asian Journal of Healthy and Science
p-ISSN: 2980-4302
e-ISSN: 2980-4310
Vol. 2 No. 7 July 2023
ANTICHOLESTEROL ACTIVITY AND MECHANISMS OF KONJAC
GLUCOMANNAN: A SYSTEMATIC REVIEW
1
Sugeng Mashudi,
2
Dian Laila Purwaningroon,
3
Yaya Sulthon Aziz,
4
Umi Farida
1,2,4
Universitas Muhammadiyah Ponorogo, Indonesia
3
Akafarma Ponorogo, Indonesia
Email: sugengmashudi@umpo.ac.id
Abstract
The traditional Chinese medicinal herb konjac glucomannan has been used for
centuries, and its active component, glucomannan, is well-known. Glucomannan is
a naturally occurring polysaccharide found in some plant species. Glucomannan's
special capacity as a dietary supplement has led to its widespread usage in clinical
settings for the treatment of obesity, high cholesterol, constipation, diabetes, and
atherosclerosis. The therapeutic impact and underlying processes in treating arterial
sclerosis illnesses have been the subject of growing study in recent years, adding to
its regulatory function in gastroenterology and metabolic syndrome. This review
aims to provide insight on the several mechanisms by which konjac glucomannan
achieves its cholesterol-lowering effect.
Keywords: konjac glucomannan; metabolic syndrome; anti-cholesterol; traditional
Chinese medicinal herb; arterial sclerosis.
INTRODUCTION
The corm of the plant Amorphophallus konjac is the source of the main polysaccharide
known as konjac glucomannan (KGM) (Devaraj et al., 2019; Zhu, 2018). A. konjac dormant
corms contain 4960% (w/w) glucomannan, 1030% (w/w) starch, 2.67% (w/w) inorganic
elements (aluminium, calcium, chromium, cobalt, iron, magnesium, manganese,
phosphorus, potassium, selenium, sodium, tin and zinc), 514% (w/w) crude protein, 35%.
Serotonin and its derivatives cis-N-(p-coumaroyl) serotonin and trans-N-(p-coumaroyl)
serotonin have also been found in fresh corm tissue (Chua et al., 2010). The health benefits
include a reduction in body fat and an increase in satiety, improved dental health, increased
development and viability of beneficial organisms in the colon, and cholesterol (sugeng
mashudi et al., 2022; Tester & Al-Ghazzewi, 2016; Zhu, 2018).
Cholesterol is a kind of steroid that is found in cell membranes and serves as a
precursor of other steroids, as well as vitamins and bile ((Zárate et al., 2016). It is also a
necessary part of the myelin that covers the nerves and lets the electrical impulses pass
through to make sure that some of the effector tissues respond in the right way (Rodriguez-
Concepcion et al., 2018). A part of cholesterol is received through diet, but the vast majority
is generated in the liver and then enters the general circulation via lipoproteins of varying
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molecular weight (Shumskaya & Wurtzel, 2013). Researchers who have earned the Nobel
Prize for their contributions to the research of cholesterol: 1) Heinrich Otto Wieland won the
Nobel Prize in Chemistry for his work on biliary acids in 1927; 2) Adolf Otto Windaus
described atheromas made of cholesterol crystals in his investigations, which earned him the
Nobel Prize in Chemistry in 1928; 3) Cholesterol production research by Konrad Bloch and
Feodor Lynen won the Nobel Prize in Physiology and Medicine in 1964; cholesterol
metabolism research by Michael S. Brown and Joseph L. Goldstein won the same honor in
1985 (Zárate et al., 2016). In the same way that Fleming obtained penicillin, the notion of
acquiring a pharmaceutical product that might be utilized in the clinic for the treatment of
hypercholesterolemia emerged. This medicine was originally called as compactin, and the
research of similar compounds became known as statins, implying a major development in
treatments; for these results, Endo was awarded the Lasker Prize in 2008(Endo, 2010).
Konjac glucomannan as Anticholesterol medication derived from konjac glucomannan for
schizophrenia (Sugeng Mashudi, et.,al, 2022; sugeng mashudi et al., 2022) and restore health
damaged by metabolic syndrome (Tran et al., 2022).
RESEARCH METHODS
This research makes use of a narrative approach to examine previous research on konjac
glucomannan that has been conducted elsewhere in the globe and published in databases,
such as ScienceDirect, Pubmed, Cochrane, and Proquest, as well as other international
journals. There is no restriction placed on the articles based on the location of the study, and
the selection of papers is done based on the inclusion and exclusion criteria. The study
excluded any publications that were deemed to be irrelevant to the topic. The terms
anticolesterol and konjac glucomannan have been used as the search terms. Each article that
is used is assessed according to a number of criteria, including keywords, limits, the precision
of the techniques used, the quality of the findings produced, the interpretation of the results,
the impact, and the conclusions.
RESULT AND DISCUSSION
Regulation of cholesterol metabolism
Both dietary cholesterol and cholesterol synthesized in the body (mostly by the
liver) contribute to total blood cholesterol levels (Endo, 2010). The former is supplied
by the latter if the needed levels are not obtained, but if the former sort of "exogenous"
cholesterol achieves the required level, the liver's synthesis function is regulated to
avoid excessive cholesterol formation. Changes in the activity of HMG-CoA
reductase, the enzyme responsible for catalyzing the conversion of HMG-CoA to
mevalonate, are the mechanism by which dietary cholesterol inhibits cholesterol
production in the liver (Endo, 2010). Modifications to reductase activity are closely
linked to changes in cholesterol synthesis. The quantity of cholesterol produced by
the liver much outweighs the amount absorbed from food, even when a lot of
cholesterol is eaten. These findings suggest that blocking HMG-CoA reductase might
be an effective strategy for lowering plasma cholesterol in humans (Endo, 2010).
Intense PPAR agonist treatment causes browning of white adipose tissue (WAT) and
improvement in WAT insulin sensitivity. Consequently, glucose metabolism
throughout the body improves. However, PPAR agonist-induced improvement in
lipid metabolism may occur without FGF21 being present (Figure 1).
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Figure 1. The Role of FGF21, a Hepatokine, in Obesity-Induced Anticholesterol
Effects Treated by PPAR Agonists Sources : (Goto, 2019)
PPAR and the Metabolism of the Liver
During fasting as well as after meals, the liver is responsible for managing the
balance of glucose and lipids in the body, in addition to the body's energy
metabolism. Enzymes that are upregulated by PPAR activity are denoted in green.
ACADM stands for medium-chain acyl-coenzyme A (CoA) dehydrogenase;
ACADVL stands for very-long chain acyl-CoA dehydrogenase; ACOX1 stands for
acyl-CoA oxidase 1; ACSL1 stands for acyl-CoA synthetase long chain family
member 1; ATP stands for adenosine triphosphate; CPT1A stands for (figure 2).
Organs express the three PPARs differently, reflecting their diverse
physiological functions (Wang et al., 2020). Hepatocytes, cardiomyocytes, proximal
renal tubular cells, and brown adipocytes express PPAR. PPAR/ is more widespread
but mostly present in skeletal muscle, skin, fat, heart, liver, and inflammatory cells.
PPAR has three splicing variant isoforms (1, 2, and 3) with different tissue
localizations despite the identical DNA binding specificity: 1 (ubiquitous), 2 (adipose
tissue), and 3. (localized in macrophages, colon, and adipose tissue). PPAR 2 has 5-
10 times more transcriptional activity than PPAR 1(Temelkova-Kurktschiev et al.,
2004). FA activates PPAR, which increases FA-oxidation, ATP generation, and
ketogenesis in nutrient-deprived states. PPAR activates multiple proteins, including
FA-binding protein 4 (FABP4, also known as aP2), which stores FAs in adipocytes
as triacylglycerol (TAG). Nutrient excess and obesity activate PPAR in the liver,
which stores FA as lipid droplets (Madsen et al., 2022; Matsusue et al., 2008;
Temelkova-Kurktschiev et al., 2004). Thus, differences in cell-specific expression,
ligands, and target genes imply that the three PPARs play different roles in liver
energy/nutrient metabolism.
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Figure 2.
The role of peroxisome proliferator-activated receptors (PPARs) in hepatic
lipid metabolism and associated alterations in NASH development: a brief
summary (red arrows)
Sources:(Wang et al., 2020)
NASH and Peroxisome Protein Activator Receptor
Hepatocytes, which are found in the liver, have more and bigger peroxisomes
than other cell types. An estimated 2% of the liver's parenchymal volume is occupied
by these structures. Hepatic peroxisomes perform - and -oxidation and ether lipid
synthesis as metabolic functions. Phytanic acid, a branched chain fatty acid, and 2-
hydroxylated fatty acids each had one of their carbon atoms removed during the -
oxidation process. The process of -oxidation results in the destruction of very long
chain fatty acids (VLCFA), dicarboxylic fatty acids (DCA), and pristanic acids
(produced from phytanic acids). The anabolic function includes the synthesis of
docosahexaenoic acid, a polyunsaturated fatty acid, and the production of mature
bile acids from cholesterol (Shao et al., 2022). Many steps of peroxisomal fatty acid
metabolism are transcriptionally regulated by PPAR. One factor in the development
of NASH is an increase in fatty acid synthesis, which may be caused by altered PPAR
expression by drastically disrupting fatty acid oxidation and triggering lipogenesis.
To reduce liver fat accumulation while maintaining elevated ex novo lipogenesis,
PPAR agonists like fenofibrate boost gene expression. As an added bonus,
fenofibrate therapy completely corrected high-fructose-induced glucose intolerance,
hepatic steatosis, and changed hepatic insulin signaling (pAkt and pGSK3).
Additionally, peroxisomes include detoxifying enzymes like catalase and superoxide
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dismutase, which neutralize reactive oxygen species (ROS) produced by other
oxidation processes. Peroxisomal-oxidation is limited by the activity of multiple
Acyl-CoA oxidases, which in turn generate H2O2. Deficiencies in peroxisomal -
oxidation and hepatic steatosis are seen in acyl-CoA oxidase null mice. D-amino acid
oxidases, 2-hydroxy acid oxidases (HAO), L-pipecolate oxidase, and alanine
glyoxylate aminotransferase all play roles in oxidative reactions that generate H2O2
(Dutta et al., 2022). Therefore, peroxisomes have two challenges: first, they must
neutralize reactive oxygen species (ROS), which are produced mostly during fatty
acid oxidation (Figure 3); and second, they must create ROS. Accelerated levels of
circulating fatty acids and increased rates of fatty acid oxidation result in a high
volume of reactive oxygen species (ROS) that need to be neutralized, suggesting that
the liver in NASH depends significantly on peroxisomes for safe ROS disposal.
Scavenging reactive oxygen species is essential for protecting against oxidative stress.
Fatty diet-induced steatosis of the liver in catalase knock-out mice leads to increased
oxidative stress and inflammation at an earlier stage than in wild-type animals.
Figire 3. Role of peroxisome and mitochondrial PPAR in lipid metabolism
Sources: (Todisco et al., 2022)
PPAR is involved in the regulation of gene expression in hepatocytes along
lipid metabolic pathways such as FABP1, which regulates the trafficking, transport,
and storage of FFA, and LCAD and MCAD, which are involved in mitochondrial -
oxidation. Lipotoxicity in NASH is produced by the accumulation of free fatty acids
in the liver, which is also induced by the mobilization of triglycerides from adipose
tissue and a decrease in PPAR activity (red arrows). Atherosclerosis and foam cell
production are both aided by dysregulation of lipoprotein metabolism, which causes
HDL levels to decline and LDL and oxidized LDL to grow.
As was previously mentioned, dietary fatty acids may stimulate PPAR in the
liver. Particularly potent PPAR activators are polyunsaturated fatty acids, which are
superior than saturated and monounsaturated fatty acids. Therefore, fish oil, which
is rich in n-3 polyunsaturated fatty acids, encourages the expression of PPAR target
genes more effectively than other common dietary oils (Todisco et al., 2022).
Increased fatty acid oxidation through a PPAR-stimulated mechanism is only one of
the many health advantages associated with the omega-3 fatty acids eicosapentaenoic
acid and docosahexaenoic acid, both of which are found in fish oils (Jump et al.,
2005). We observed that certain, food-based fatty acids, such as oxo fatty acids and
branched fatty acids, had considerable PPAR ligand activity, and that some of these
fatty acids also demonstrated PPAR ligand activity (An et al., 2018). Twelve fatty
acids generated from linoleic acid were analyzed for their PPARs ligand activity
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(Hirata et al., 2015). These modified unique fatty acids, when included in the diet,
helped alleviate obesity-related metabolic abnormalities in mouse models of obesity.
Researchers have discovered that lactic acid bacteria in the stomach may convert
polyunsaturated fats like linoleic acid into a variety of other fatty acids via a process
called "saturated metabolism" (Kishino et al., 2013). This research suggests that
metabolites of dietary fatty acids generated by lactic acid bacteria in the gut may
function as PPARs ligands in the host and play a role in the regulation of host energy
metabolism. In addition, it was shown that 10-oxo-11(E)- octadecenoic acid
significantly suppresses inflammation in obese adipose tissue, which is one of the key
causes of obesity-related metabolic issues due to the interaction between
hypertrophied adipocytes and activated macrophages (Yang et al., 2017).
We observed that the isoprenoid farnesol, which is present in many different
types of fruits and berries (including apricots, peaches, plums, blueberries,
cranberries, raspberries, and strawberries), is an effective PPAR activator using a
luciferase reporter assay. Hyperglycemia, glucose intolerance, insulin resistance, and
hepatic triglyceride levels were significantly reduced in obese KK-Ay mice fed a diet
containing 0.5% farnesol. Increased mRNA expression of PPAR target genes
involved in fatty acid oxidation in the liver was seen after a high-farnisol diet.
Experiments with PPAR-deficient animals showed that PPAR activity was required
for the effects of a farnesol-containing diet on blood glucose and the activation of
genes involved in fatty acid oxidation. On the other hand, a meal high in farnesol
inhibited PPAR-dependent hepatic lipid biosynthesis (Li et al., 2007).
Conversely, farnesol did not affect the mRNA expression of PPAR target genes
in WAT. This research suggests that farnesol may ameliorate metabolic issues in
mice through PPAR-dependent and -independent pathways (Figure 4). The PPARs
LBD has a large pocket where the ligand molecule is bound. Consequently, their
ligands have been narrowed down to a few of naturally occurring and food-based
compounds. Recognizing PPAR dietary ligands and incorporating them into one's
diet may be helpful in the fight against obesity due to the PPARs' central function in
coordinating whole-body glucose and lipid metabolism.
Figure 4. Consumption of farnesol controls glucose and lipid metabolism
Sources: (Goto et al., 2011).
Fatty acid oxidation was boosted by farnesol in the diet because of PPAR
activation, whereas hepatic TG synthesis was lowered because of FXR-SHP-SREBP-
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1c activation. The combined action of farnesol in the liver on hepatic steatosis and
hyperglycemia suggests that it may help ameliorate these obesity-related metabolic
disorders (Rizzo, 2014). The abbreviations for these proteins are as follows: CPT1 =
carnitine palmitoyl transferase 1, AOX = acyl-CoA oxidase, ACS = acyl-CoA
synthase, UCP2 = uncoupling protein 2, FXR = farnesoid X receptor, SHP = small
heterodimer partner, and SREBP-1c = sterol regulatory elementbinding protein-1c.
.
CONCLUSION
Amorphophallus konjac's corm produces konjac glucomannan (KGM), the primary
polysaccharide. Health advantages include a decrease in body fat and satiety, better dental
health, enhanced colonic beneficial organism formation and viability, and cholesterol.
Anticholesterol medicine developed from konjac glucomannan for schizophrenia.
REFERENCES
Chua, M., Baldwin, T. C., Hocking, T. J., & Chan, K. (2010). Traditional Uses And
Potential Health Benefits Of Amorphophallus Konjac K. Koch Ex N.E.Br.
Journal Of Ethnopharmacology, 128(2), 268278.
Https://Doi.Org/10.1016/J.Jep.2010.01.021
Devaraj, R. D., Reddy, C. K., & Xu, B. (2019). Health-Promoting Effects Of Konjac
Glucomannan And Its Practical Applications: A Critical Review. International
Journal Of Biological Macromolecules, 126, 273281.
Https://Doi.Org/10.1016/J.Ijbiomac.2018.12.203
Dutta, R. K., Lee, J. N., Maharjan, Y., Park, C., Choe, S.-K., Ho, Y.-S., Kwon, H.
M., & Park, R. (2022). Catalase-Deficient Mice Induce Aging Faster Through
Lysosomal Dysfunction. Cell Communication And Signaling: CCS, 20(1),
192. Https://Doi.Org/10.1186/S12964-022-00969-2
Endo, A. (2010). A Historical Perspective On The Discovery Of Statins. Proceedings
Of The Japan Academy. Series B, Physical And Biological Sciences, 86(5),
484493. Https://Doi.Org/10.2183/Pjab.86.484
Goto, T. (2019). A Review Of The Studies On Food-Derived Factors Which
Regulate Energy Metabolism Via The Modulation Of Lipid-Sensing Nuclear
Receptors. Bioscience, Biotechnology And Biochemistry, 83(4), 579588.
Https://Doi.Org/10.1080/09168451.2018.1559025
Goto, T., Kim, Y. Il, Funakoshi, K., Teraminami, A., Uemura, T., Hirai, S., Lee, J.
Y., Makishima, M., Nakata, R., Inoue, H., Senju, H., Matsunaga, M., Horio,
F., Takahashi, N., & Kawada, T. (2011). Farnesol, An Isoprenoid, Improves
Metabolic Abnormalities In Mice Via Both Pparα-Dependent And -
Independent Pathways. American Journal Of Physiology - Endocrinology And
Metabolism, 301(5). Https://Doi.Org/10.1152/Ajpendo.00061.2011
Madsen, M. S., Broekema, M. F., Madsen, M. R., Koppen, A., Borgman, A.,
Gräwe, C., Thomsen, E. G. K., Westland, D., Kranendonk, M. E. G.,
Koerkamp, M. G., Hamers, N., Bonvin, A. M. J. J., Pittol, J. M. R., Natarajan,
K. N., Kersten, S., Holstege, F. C. P., Monajemi, H., Van Mil, S. W. C.,
Vermeulen, M., Kalkhoven, E. (2022). Pparγ Lipodystrophy Mutants
Reveal Intermolecular Interactions Required For Enhancer Activation. Nature
Communications, 13(1), 7090. Https://Doi.Org/10.1038/S41467-022-34766-
9
https://ajhsjournal.ph/index.php/gp 312
Matsusue, K., Kusakabe, T., Noguchi, T., Takiguchi, S., Suzuki, T., Yamano, S., &
Gonzalez, F. J. (2008). Hepatic Steatosis In Leptin-Deficient Mice Is Promoted
By The Pparγ Target Gene Fsp27. Cell Metabolism, 7(4), 302311.
Https://Doi.Org/10.1016/J.Cmet.2008.03.003
Rodriguez-Concepcion, M., Avalos, J., Bonet, M. L., Boronat, A., Gomez-Gomez,
L., Hornero-Mendez, D., Limon, M. C., Meléndez-Martínez, A. J., Olmedilla-
Alonso, B., & Palou, A. (2018). A Global Perspective On Carotenoids:
Metabolism, Biotechnology, And Benefits For Nutrition And Health. Progress
In Lipid Research, 70, 6293.
Shao, G., He, T., Mu, Y., Mu, P., Ao, J., Lin, X., Ruan, L., Wang, Y., Gao, Y., Liu,
D., Zhang, L., & Chen, X. (2022). The Genome Of A Hadal Sea Cucumber
Reveals Novel Adaptive Strategies To Deep-Sea Environments. Iscience,
25(12), 105545. Https://Doi.Org/10.1016/J.Isci.2022.105545
Shumskaya, M., & Wurtzel, E. T. (2013). The Carotenoid Biosynthetic Pathway:
Thinking In All Dimensions. Plant Science: An International Journal Of
Experimental Plant Biology, 208, 5863.
Https://Doi.Org/10.1016/J.Plantsci.2013.03.012
Sugeng Mashudi, Tukimin Bin Sansuwito, Dian Laila Purwaningroom, F. I. P.
(2022). Occupational Balance Improves Subjective Health And Quality Of Life
Family With Mental Health Disorders. Journal Of Intellectual Dissability
Diagnosis And Treatment And Treatment, 10(5), 232237.
Https://Doi.Org/Https://Doi.Org/10.6000/2292-2598.2022.10.05.4
Sugeng Mashudi, Dhianita, Aziz, & Syafira. (2022). Effects Of Konjac
Glucomannan On Blood Profile In Schizophrenia With Hyperglycemia: Pra
Eksperimental Study. International Journal Of Public Health, 1(6).
Temelkova-Kurktschiev, T., Hanefeld, M., Chinetti, G., Zawadzki, C., Haulon, S.,
Kubaszek, A., Koehler, C., Leonhardt, W., Staels, B., & Laakso, M. (2004).
Ala12Ala Genotype Of The Peroxisome Proliferator-Activated Receptor
Gamma2 Protects Against Atherosclerosis. The Journal Of Clinical
Endocrinology And Metabolism, 89(9), 42384242.
Https://Doi.Org/10.1210/Jc.2003-032120
Tester, R. F., & Al-Ghazzewi, F. H. (2016). Beneficial Health Characteristics Of
Native And Hydrolysed Konjac (Amorphophallus Konjac) Glucomannan.
Journal Of The Science Of Food And Agriculture, 96(10), 32833291.
Https://Doi.Org/Https://Doi.Org/10.1002/Jsfa.7571
Todisco, S., Santarsiero, A., Convertini, P., De Stefano, G., Gilio, M., Iacobazzi,
V., & Infantino, V. (2022). PPAR Alpha As A Metabolic Modulator Of The
Liver: Role In The Pathogenesis Of Nonalcoholic Steatohepatitis (NASH).
Biology, 11(5). Https://Doi.Org/10.3390/Biology11050792
Tran, T. N., Tran, H. D., Tran-Huu, T. T., Tran, D. M., & Tran, Q. N. (2022). A
Cross-Sectional Study Of Serum Ferritin Levels In Vietnamese Adults With
Metabolic Syndrome. Diabetes, Metabolic Syndrome And Obesity: Targets
And Therapy, 15(May), 15171523.
Https://Doi.Org/10.2147/DMSO.S360689
Wang, Y., Nakajima, T., Gonzalez, F. J., & Tanaka, N. (2020). Ppars As Metabolic
Regulators In The Liver: Lessons From Liver-Specific PPAR-Null Mice.
International Journal Of Molecular Sciences, 21(6).
Https://Doi.Org/10.3390/Ijms21062061
https://ajhsjournal.ph/index.php/gp 313
Zárate, A., Manuel-Apolinar, L., Basurto, L., De La Chesnaye, E., & Saldívar, I.
(2016). Cholesterol And Atherosclerosis. Historical Considerations And
Treatment. Archivos De Cardiologia De Mexico, 86(2), 163169.
Https://Doi.Org/10.1016/J.Acmx.2015.12.002
Zhu, F. (2018). Modifications Of Konjac Glucomannan For Diverse Applications.
Food Chemistry, 256(November 2017), 419426.
Https://Doi.Org/10.1016/J.Foodchem.2018.02.151
Copyright holders:
Sugeng Mashudi, Dian Laila Purwaningroon, Yahya Sulthon Aziz,
Umi Farida (2023)
First publication right:
AJHS - Asian Journal of Healthy and Science
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