Guggulsterone is a

phytosteroid Phytosteroids, also known as plant steroids, are natural product, naturally occurring steroids that are found in plants. Examples include digoxin, digitoxin, diosgenin, and guggulsterone, as well as phytosterols like β-sitosterol. Industrial ...

found in the

resin A resin is a solid or highly viscous liquid that can be converted into a polymer. Resins may be biological or synthetic in origin, but are typically harvested from plants. Resins are mixtures of organic compounds, predominantly terpenes. Commo ...

of the

guggul ''Commiphora wightii'', with common names Indian bdellium-tree, gugal, guggal, guggul, gugul, or mukul myrrh tree, is a flowering plant in the family Burseraceae, which produces a fragrant resin called gugal, guggul or gugul, that is used in i ...

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 i ...

, ''E''-guggulsterone and ''Z''-guggulsterone. In humans, it acts as an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.farnesoid X receptor The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4), is a nuclear receptor that is encoded by the ''NR1H4'' gene in humans. Function FXR is expressed at high level ...

, which was once believed to result in decreased

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

synthesis in the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

. 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 density ...

("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 a person'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 ( ...

s. Guggulsterone was also found to have interactions with the viral ADP ribose phosphatase enzyme of

SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional nam ...

and has been proposed as a potential candidate for the development of therapeutics for the treatment of COVID-19. Guggulsterone is a broad-spectrum

ligand In coordination chemistry, a ligand is an ion or molecule with a 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 el ...

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 An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.Progesterone receptor The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone. In humans, PR is encoded by a single ''PGR'' gene resi ...

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

(K_i = 201 nM) *

Glucocorticoid receptor The glucocorticoid receptor (GR or GCR) also known by its gene name ''NR3C1'' ( nuclear receptor subfamily 3, group C, member 1) is the steroid receptor for glucocorticoids such as cortisol. The GR is expressed in almost every cell in the bod ...

antagonist (K_i = 224 nM) *

Androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...

antagonist (K_i = 240 nM) *

Estrogen receptor Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

(K_i > 5 μM; EC₅₀ > 5 μM) *

Farnesoid X receptor The bile acid receptor (BAR), also known as farnesoid X receptor (FXR) or NR1H4 (nuclear receptor subfamily 1, group H, member 4), is a nuclear receptor that is encoded by the ''NR1H4'' gene in humans. Function FXR is expressed at high level ...

antagonist ( IC₅₀ = 5–50 μM) * Pregnane X receptor 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 animals, as model organisms, in experiments that seek answers to scientific and medical questions. This approach can be contrasted ...

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%. H ...

of 42.9% after

oral administration Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

in rats, with a

half-life Half-life is a mathematical and scientific description of exponential or gradual decay. Half-life, half life or halflife may also refer to: Film * Half-Life (film), ''Half-Life'' (film), a 2008 independent film by Jennifer Phang * ''Half Life: ...

of around 10 hours in this species, indicating a good

pharmacokinetic Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific subs ...

profile.

References

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

, 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