Guggulsterone is a phytosteroid found in the

resin In polymer chemistry and materials science, resin is a solid or highly viscous substance of plant or synthetic origin that is typically convertible into polymers. Resins are usually mixtures of organic compounds. This article focuses on n ...

of the guggul plant, ''Commiphora mukul''. Guggulsterone can exist as either of two

stereoisomers In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms ...

, ''E''-guggulsterone and ''Z''-guggulsterone. In humans, it acts as an antagonist of the farnesoid X receptor, which was once believed to result in decreased

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

synthesis in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

. Several studies have been published that indicate no overall reduction in total cholesterol occurs using various dosages of guggulsterone, and levels of

low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall dens ...

("bad cholesterol") increased in many people. Nevertheless, guggulsterone is an ingredient in many

nutritional supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...

s. Guggulsterone was also found to have interactions with the viral Adipose Ribose Phosphatase enzyme of SARS-CoV2 and can prove to be a potential candidate for the development of therapeutics for the treatment of COVID19.Kciuk, M.; Mujwar, S.; Rani, I.; Munjal, K.; Gielecińska, A.; Kontek, R.; Shah, K. Computational Bioprospecting Guggulsterone against ADP Ribose Phosphatase of SARS-CoV-2. Molecules 2022, 27, 8287. https://doi.org/10.3390/molecules27238287 Guggulsterone is a broad-spectrum

ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...

steroid hormone receptor Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors (typically cytoplasmic or nuclear) and initiate signal transduction for steroid hormones which ...

s, and is known to possess the following activities: *

Mineralocorticoid receptor The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the ''NR3C2'' gene that is located on chromosome 4q31 ...

antagonist (K_i = 39 nM) * Progesterone receptor

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...

(K_i = 201 nM) *

Glucocorticoid receptor The glucocorticoid receptor (GR, or GCR) also known as NR3C1 (nuclear receptor subfamily 3, group C, member 1) is the receptor to which cortisol and other glucocorticoids bind. The GR is expressed in almost every cell in the body and regulates ...

antagonist (K_i = 224 nM) * Androgen receptor antagonist (K_i = 240 nM) *

Estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen (17β-estradiol). Two classes of ER exist: nuclear estrogen receptors ( ERα and ERβ), which are members of the ...

agonist (K_i > 5 μM; EC₅₀ > 5 μM) * Farnesoid X receptor antagonist ( IC₅₀ = 5–50 μM) *

Pregnane X receptor In the field of molecular biology, the pregnane X receptor (PXR), also known as the steroid and xenobiotic sensing nuclear receptor (SXR) or nuclear receptor subfamily 1, group I, member 2 (NR1I2) is a protein that in humans is encoded by the ' ...

agonist (EC₅₀ = 2.4 μM ((Z)-isomer)) Guggulsterone has been found in

animal research Animal testing, also known as animal experimentation, animal research, and ''in vivo'' testing, is the use of non-human animals in experiments that seek to control the variables that affect the behavior or biological system under study. This ...

to be orally active; it has an absolute

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...

of 42.9% after

oral administration Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are ...

in rats, with a

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...

of around 10 hours in this species, indicating a good pharmacokinetic profile.

References

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Pharmacodynamics Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms ...

, titlestyle = background:#ccccff , list1 = {{Androgen receptor modulators {{Estrogen receptor modulators {{FXR and LXR modulators {{Glucocorticoid receptor modulators {{Mineralocorticoid receptor modulators {{Progesterone receptor modulators {{Xenobiotic-sensing receptor modulators Antiglucocorticoids Antimineralocorticoids Estrogens Pregnane X receptor agonists Pregnanes Progestogens Selective progesterone receptor modulators Steroidal antiandrogens