Sennosides

Identification

Summary

Sennosides is a laxative used to treat constipation.

Brand Names
Colace, EX-lax Chocolated, EX-lax Maximum Relief Formula, EX-lax Regular Strength Pills, Laxacin, Little Tummys Laxative Drops, Perdiem Overnight, Peri-colace Reformulated Feb 2008, Senexon, Senexon S, Senna Lax, Senna-time, Senokot, Senokot-S
Generic Name
Sennosides
DrugBank Accession Number
DB11365
Background

Sennosides (also known as senna glycoside or senna) is a medication used to treat constipationLabel12 and empty the large intestine before surgery. The medication is taken by mouth or via the rectumLabel. It typically begins working in minutes when given by rectum and within twelve hours when given by mouthLabel. It is a weaker laxative than bisacodyl or castor oil11. Sennoside A, one of the sennosides present in the laxative medication, has recently proven effective in inhibiting the ribonuclease H (RNase H) activity of human immunodeficiency virus (HIV) reverse transcriptase 1.

Type
Small Molecule
Groups
Experimental
Structure
Thumb
Weight
Average: 862.746
Monoisotopic: 862.195643624
Chemical Formula
C42H38O20
Synonyms
  • Senna glycosides
  • Sennoside
  • Sennosides

Pharmacology

Indication

For the over the counter treatment of constipationLabel12.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Senna stimulates peristalsis and increases fecal water content to increase motility of feces through the large intestine6,2,12.

Mechanism of action

Sennoside A and B, the components of senna, are metabolized by gut bacteria into the active metabolite rheinanthrone Rheinanthrone2. Rheinanthrone Rheinanthrone appears to increase cyclooxegenase 2 (COX2) expression in macrophage cells leading to an increase in prostaglandin E2 (PGE2)2. This increase in PGE2 is associated with a decrease in aquaporin 3 expression in mucosal epithelial cells of the large intestine2. A decrease in aquaporin 3 expression likely produces the laxative effect by restricting water reabsorption by the large intestine thereby increasing fecal water content2. The exact mechanism by which rheinanthrone increases COX2 expression is unknown2. Rheinanthrone Rheinanthrone also stimulates peristalsis in the large intestine although the mechanism behind this effect is unknown6. Rhein Rhein, another active metabolite is thought to excite submucosal acetylcholinergic neurons resulting in increased chloride and prostaglandin secretion8,9. The movement of chloride ions into the large intestine would also help to draw water into the lumen9.

TargetActionsOrganism
AAquaporin-3
inhibitor
Humans
UReverse transcriptase/RNaseH
inhibitor
Human immunodeficiency virus 1
Absorption

<10% is absorbed from the gut mostly in the form of the active metabolite rheinanthrone [Rheinanthrone](https://go.drugbank.com/drugs/DB13175)12.

Volume of distribution

The volume of distribution of radiolabelled intravenous sennoside B in rats was 0.802±0.124L/kg10.

Protein binding

Because sennosides are ingested and their action occurs in the gut, it is generally not thought to be protein bound2.

Metabolism

Sennosides A and B are metabolised to sennidins A and B by gut bacteria6. Sennidins A and B are further metabolized to rheinanthrone Rheinanthrone by gut bacteria using beta-glucosidase2. Rheinanthrone Rheinanthrone is absorbed into systemic circulation where 2.6% is metabolized to rhein Rhein and sennidins A and B via oxidation4,7,2. Rheinanthrone Rheinanthrone is the major active metabolite of sennosides A and B which produces the laxative effect of the medication2. Rhein Rhein is also an active metabolite known to have many protective effects8.

Hover over products below to view reaction partners

Route of elimination

3-6% of metabolites are excreted in urine with some in bile. >90% of sennosides are excreted in the feces as polymers with 2-6% of the parent compounds excreted unchanged12.

Half-life

The half life of radiolabelled intravenous sennoside B in rats was 8.568±0.651h10.

Clearance

The clearance of radiolabelled intravenous sennoside B in rats was 0.065±0.007L/h/kg10.

Adverse Effects
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Toxicity

Senna causes increased amounts of apoptosis in the large intestine shortly after use due to upregulated p53 activity3. This is normally reversed after 18 hours however chronic use has been shown to be associated with p53 resistance and potential carcinogenicity leading to colon cancer3. The LD50 value in rats was 5000mg/kg. Subacute studies in rats receiving 20mg/kg and dogs receiving 500mg/kg did not produce signs of toxicity5. Tests for mutagenicity and reproductive toxicity do not indicate toxic effects5.

Sennosides are not recommended for use in pregnancy due to genotoxic risks associated with chemically similar compounds12. The active metabolite of sennosides is excreted in breast milk, though there are no reports of the laxitive effect in breast fed babies12. There is no data on the effects of sennosides on fertility12.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Sennosides.
AclidiniumThe therapeutic efficacy of Sennosides can be decreased when used in combination with Aclidinium.
AlfentanilThe therapeutic efficacy of Sennosides can be decreased when used in combination with Alfentanil.
AlloinThe risk or severity of adverse effects can be increased when Sennosides is combined with Alloin.
AmantadineThe therapeutic efficacy of Sennosides can be decreased when used in combination with Amantadine.
AmilorideThe risk or severity of adverse effects can be increased when Amiloride is combined with Sennosides.
AmiodaroneThe therapeutic efficacy of Sennosides can be decreased when used in combination with Amiodarone.
AmitriptylineThe therapeutic efficacy of Sennosides can be decreased when used in combination with Amitriptyline.
AmlodipineThe therapeutic efficacy of Sennosides can be decreased when used in combination with Amlodipine.
AmobarbitalThe therapeutic efficacy of Sennosides can be decreased when used in combination with Amobarbital.
Interactions
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Food Interactions
  • Avoid natural licorice. Licorice root can induce hypokalemia in patients taking sennosides.

Products

Products
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Product Ingredients
IngredientUNIICASInChI Key
Sennosides A and B1B5FPI42EN62211-03-4Not applicable
Product Images
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Agarol Extra Strength Chewable Laxative TabletsTablet25 mgOralNumark Laboratories, Inc.2000-08-212009-07-31Canada flag
Agarol With SennosidesLiquid25 mg / 15 mLOralNumark Laboratories, Inc.1999-06-302009-07-31Canada flag
AgoralLiquid8.3 mg/5mLOralNumark Brands, Inc1942-05-052016-10-18US flag
Assured Natural LaxativeTablet, coated8.6 mg/1OralSpirit Pharmaceuticals LLC2016-08-122016-07-28US flag
BEKUNIS LAXATIVE DRAGEES (ENTERIC COATED TABLET)Tablet, coatedOralDKSH MALAYSIA SDN BHD2020-09-08Not applicableMalaysia flag
Bekunis Natures Gentle Laxative Herbal TeaExtract23 mg/1gOralRoha Arzneimittel Gmbh2011-03-21Not applicableUS flag
Bekunis Natures Gentle Laxative Instant TeaPowder20 mg/0.5gOralRoha Arzneimittel Gmbh2011-03-21Not applicableUS flag
Bekunis Natures Gentle Stimulant LaxativeTablet, sugar coated20 mg/1OralRoha Arzneimittel Gmbh2011-02-10Not applicableUS flag
Best Choice SennaTablet8.6 mg/1OralBest Choice (Valu Merchandisers Company)2012-05-182019-12-31US flag
CAREALL SennosidesTablet8.6 mg/1OralNew World Imports2016-04-18Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
2 In 1laxative Stool Softener and Stiulant LaxativeSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)Tablet, coatedOralRite Aid2020-06-01Not applicableUS flag
2 In 1laxative Stool Softener and Stiulant LaxativeSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)Tablet, coatedOralRite Aid2020-06-01Not applicableUS flag
BEKUNIS 3 MG/5 MG KAPLI TABLET, 30 ADETSennosides (5 mg) + Bisacodyl (3 mg)Tablet, film coatedOralABDİ İBRAHİM İLAÇ SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag
Bekunis DrageesSennosides (60 mg) + Sennosides (20 mg) + Sennosides (25 mg) + Bisacodyl (5 mg)TabletOralRoha Arzneimittel Gmbh1974-12-312009-07-02Canada flag
Bekunis DrageesSennosides (60 mg) + Sennosides (20 mg) + Sennosides (25 mg) + Bisacodyl (5 mg)TabletOralRoha Arzneimittel Gmbh1974-12-312009-07-02Canada flag
Bekunis DrageesSennosides (60 mg) + Sennosides (20 mg) + Sennosides (25 mg) + Bisacodyl (5 mg)TabletOralRoha Arzneimittel Gmbh1974-12-312009-07-02Canada flag
C Ottways Lax TabSennosides (28 mg) + Aloe Vera Leaf (132 mg) + Capsicum (19 mg) + Frangula purshiana bark (28 mg) + Ginger (9 mg) + Glycyrrhiza glabra (28 mg)TabletOralC Ottway Herbalist1950-12-311997-06-13Canada flag
CAREALL Senna-S LaxativeSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)TabletOralNew World Imports, Inc.2016-04-182022-06-01US flag
CennlacsSennosides (726 mg) + Glycyrrhiza glabra (182 mg)PowderOralWestward Distributors1983-12-311997-05-30Canada flag
CholasynSennosides (12 mg) + Frangula purshiana bark (50 mg)TabletOralRolmex International Inc.1998-06-292001-08-14Canada flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Medi-laxx Rx Stool Softener and LaxativeSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)TabletOralTwo Hip Consulting, Llc2014-12-052016-04-11US flag
Senna GenSennosides (8.6 mg/1)TabletOralCardinal Health2011-06-072011-06-30US flag
Senna PlusSennosides A and B (8.6 mg/1) + Docusate sodium (50 mg/1)Tablet, film coatedOralCardinal Health2010-01-14Not applicableUS flag
Senna PlusSennosides (8.6 mg/1) + Docusate sodium (50 ug/1)TabletOralAmerincan Health Packaging2004-10-282014-08-31US flag
Senna PlusSennosides A and B (8.6 mg/1) + Docusate sodium (50 mg/1)Tablet, film coatedOralMajor Pharmaceuticals2010-01-142020-08-31US flag
Senna PlusSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)Tablet, film coatedOralCardinal Health2010-01-142014-10-31US flag
Senna-SSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)TabletOralCardinal Health2011-06-032012-05-31US flag
Senna-SSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)Tablet, coatedOralPld Acquisitions Llc Dba Avéma Pharma Solutions2010-01-022017-02-28US flag
Sennosides and Docusate SodiumSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)TabletOralMcKesson Packaging Services a business unit of McKesson Corporation2007-10-11Not applicableUS flag
Stool SoftenerSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)Tablet, coatedOralPld Acquisitions Llc Dba Avéma Pharma Solutions2010-01-022017-02-28US flag

Categories

ATC Codes
A06AB56 — Senna glycosides, combinationsA06AB06 — Senna glycosides
Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
9VK7V8762D
CAS number
517-43-1
InChI Key
IPQVTOJGNYVQEO-UHFFFAOYSA-N
InChI
InChI=1S/C42H38O20/c43-11-23-31(47)35(51)37(53)41(61-23)59-21-5-1-3-15-25(17-7-13(39(55)56)9-19(45)27(17)33(49)29(15)21)26-16-4-2-6-22(60-42-38(54)36(52)32(48)24(12-44)62-42)30(16)34(50)28-18(26)8-14(40(57)58)10-20(28)46/h1-10,23-26,31-32,35-38,41-48,51-54H,11-12H2,(H,55,56)(H,57,58)
IUPAC Name
4,4'-dihydroxy-10,10'-dioxo-5,5'-bis({[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy})-9H,9'H,10H,10'H-[9,9'-bianthracene]-2,2'-dicarboxylic acid
SMILES
OCC1OC(OC2=C3C(=O)C4=C(C=C(C=C4O)C(O)=O)C(C4C5=CC=CC(OC6OC(CO)C(O)C(O)C6O)=C5C(=O)C5=C4C=C(C=C5O)C(O)=O)C3=CC=C2)C(O)C(O)C1O

References

General References
  1. Esposito F, Carli I, Del Vecchio C, Xu L, Corona A, Grandi N, Piano D, Maccioni E, Distinto S, Parolin C, Tramontano E: Sennoside A, derived from the traditional chinese medicine plant Rheum L., is a new dual HIV-1 inhibitor effective on HIV-1 replication. Phytomedicine. 2016 Nov 15;23(12):1383-1391. doi: 10.1016/j.phymed.2016.08.001. Epub 2016 Aug 10. [Article]
  2. Kon R, Ikarashi N, Nagoya C, Takayama T, Kusunoki Y, Ishii M, Ueda H, Ochiai W, Machida Y, Sugita K, Sugiyama K: Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract. J Ethnopharmacol. 2014 Feb 27;152(1):190-200. doi: 10.1016/j.jep.2013.12.055. Epub 2014 Jan 8. [Article]
  3. van Gorkom BA, Karrenbeld A, van der Sluis T, Zwart N, de Vries EG, Kleibeuker JH: Apoptosis induction by sennoside laxatives in man; escape from a protective mechanism during chronic sennoside use? J Pathol. 2001 Aug;194(4):493-9. [Article]
  4. Dreessen M, Eyssen H, Lemli J: The metabolism of sennosides A and B by the intestinal microflora: in vitro and in vivo studies on the rat and the mouse. J Pharm Pharmacol. 1981 Oct;33(10):679-81. [Article]
  5. Mengs U: Toxic effects of sennosides in laboratory animals and in vitro. Pharmacology. 1988;36 Suppl 1:180-7. [Article]
  6. Hardcastle JD, Wilkins JL: The action of sennosides and related compounds on human colon and rectum. Gut. 1970 Dec;11(12):1038-42. [Article]
  7. de Witte P, Lemli J: Metabolism of 14C-rhein and 14C-rhein anthrone in rats. Pharmacology. 1988;36 Suppl 1:152-7. [Article]
  8. Zhou YX, Xia W, Yue W, Peng C, Rahman K, Zhang H: Rhein: A Review of Pharmacological Activities. Evid Based Complement Alternat Med. 2015;2015:578107. doi: 10.1155/2015/578107. Epub 2015 Jun 22. [Article]
  9. Frieling T, Rupprecht C, Schemann M: Rhein stimulates electrogenic chloride secretion by activation of submucosal neurons in guinea pig colon. Pharmacology. 1993 Oct;47 Suppl 1:70-6. [Article]
  10. Zhang D, Huang D, Ji Y, Jiang C, Li Y, Gao M, Yao N, Liu X, Shao H, Jing S, Ni Y, Yin Z, Zhang J: Experimental evaluation of radioiodinated sennoside B as a necrosis-avid tracer agent. J Drug Target. 2015 Feb;23(2):180-90. doi: 10.3109/1061186X.2014.971328. Epub 2014 Oct 20. [Article]
  11. Portalatin M, Winstead N: Medical management of constipation. Clin Colon Rectal Surg. 2012 Mar;25(1):12-9. doi: 10.1055/s-0032-1301754. [Article]
  12. Senokot Tablet Product Information [Link]
Human Metabolome Database
HMDB34317
KEGG Compound
C10404
PubChem Substance
347911200
ChemSpider
5010
BindingDB
92481
RxNav
36387
ChEBI
9112
ChEMBL
CHEMBL54481
Wikipedia
Senna_glycoside
AHFS Codes
  • 56:12.00 — Cathartics and Laxatives
  • 92:01.00* — Herbs and Natural Products
FDA label
Download (335 KB)
MSDS
Download (34.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableColonoscopy Preparation1
4CompletedTreatmentColonoscopy Preparation1
4CompletedTreatmentConstipation1
4TerminatedPreventionConstipation1
4TerminatedSupportive CareConstipation / Malignancies1
4Unknown StatusTreatmentConstipation / Peritoneal dialysis complication1
3RecruitingPreventionMalignant Neoplasm of Colon1
3RecruitingPreventionRectal Cancer Surgery1
2CompletedTreatmentFunctional Constipation / Gastrointestinal Disorder1
2TerminatedTreatmentDiabetic Gastroparesis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral25 mg
LiquidOral25 mg / 15 mL
GranuleOral
LiquidOral8.3 mg/5mL
Powder, for suspensionOral
ExtractOral23 mg/1g
PowderOral20 mg/0.5g
Tablet, sugar coatedOral20 mg/1
Powder1 kg/1kg
Powder20 kg/20kg
LiquidOral.7 mg / mL
Tablet, chewableOral8.6 mg/1
Bar, chewableOral15 mg/1
Tablet, chewableOral15 mg/1
LiquidOral25 mg/15mL
PillOral15 mg/1
Tablet, chewableOral
Granule, effervescentOral
Granule, for solutionOral
LiquidOral
TabletOral8.6 mg / tab
TabletOral12 mg
TabletOral175 mg
LiquidOral
LiquidOral100 g
ExtractOral1000 mg/1g
PowderOral1000 mg/1g
KitOral
CapsuleOral
TabletOral12 mg/1
Tablet, chewableOral3 mg/1
Tablet, sugar coatedOral25 mg/1
TabletOral
PillOral25 mg/1
TabletOral15 mg
Tablet, coatedOral15 mg/1
Tablet, sugar coatedOral15 mg/1
TabletOral25 mg/1
TabletOral
LiquidOral8.8 mg/1mL
Tablet, coatedOral25 mg/1
TabletOral8.6 mg
TabletOral15 mg/1
CapsuleOral15 mg
PowderOral
Granule
LiquidOral10.5 mg / pck
Tablet, coatedOral
CapsuleOral8.6 mg/1
Capsule, gelatin coatedOral8.6 mg/1
LiquidOral415.36 mg/236mL
SyrupOral417.12 mg/237mL
TabletOral250 mg
Tablet, film coatedOral8.6 mg/1
Tablet, coatedOral8.6 mg/1
ExtractOral0.4 g
Capsule, gelatin coatedOral
TabletOral8.6 mg/1
LiquidOral8.8 mg/5mL
Tablet, film coatedOral
Tablet, delayed release
SyrupOral8.8 mg/5mL
Capsule, liquid filledOral17.2 mg/17.21
Capsule, liquid filledOral17.2 mg/1
Tablet, film coatedOral17.2 mg/1
PowderOral326 mg
SuppositoryRectal652 mg
PillOral
TabletOral17.2 mg/1
JellyOral5 mg / 7 g
CapsuleOral8.3 mg/1
SyrupOral
Granule, for solutionOral
Tablet, coatedOral
Powder, for solutionOral
Powder, for solutionOral
LiquidOral1.7 mg / mL
PowderOral3.5 g
SolutionOral
TabletOral7.5 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.753 mg/mLALOGPS
logP0.94ALOGPS
logP1.19ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)3.23ChemAxon
pKa (Strongest Basic)-4ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count20ChemAxon
Hydrogen Donor Count12ChemAxon
Polar Surface Area347.96 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity205.44 m3·mol-1ChemAxon
Polarizability81.49 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Water channel required to promote glycerol permeability and water transport across cell membranes. Acts as a glycerol transporter in skin and plays an important role in regulating SC (stratum corneum) and epidermal glycerol content. Involved in skin hydration, wound healing, and tumorigenesis. Provides kidney medullary collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. Slightly permeable to urea and may function as a water and urea exit mechanism in antidiuresis in collecting duct cells. It may play an important role in gastrointestinal tract water transport and in glycerol metabolism (By similarity).
Specific Function
Glycerol channel activity
Gene Name
AQP3
Uniprot ID
Q92482
Uniprot Name
Aquaporin-3
Molecular Weight
31543.605 Da
References
  1. Kon R, Ikarashi N, Nagoya C, Takayama T, Kusunoki Y, Ishii M, Ueda H, Ochiai W, Machida Y, Sugita K, Sugiyama K: Rheinanthrone, a metabolite of sennoside A, triggers macrophage activation to decrease aquaporin-3 expression in the colon, causing the laxative effect of rhubarb extract. J Ethnopharmacol. 2014 Feb 27;152(1):190-200. doi: 10.1016/j.jep.2013.12.055. Epub 2014 Jan 8. [Article]
Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Rna-dna hybrid ribonuclease activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72547
Uniprot Name
Reverse transcriptase/RNaseH
Molecular Weight
65223.615 Da
References
  1. Esposito F, Carli I, Del Vecchio C, Xu L, Corona A, Grandi N, Piano D, Maccioni E, Distinto S, Parolin C, Tramontano E: Sennoside A, derived from the traditional chinese medicine plant Rheum L., is a new dual HIV-1 inhibitor effective on HIV-1 replication. Phytomedicine. 2016 Nov 15;23(12):1383-1391. doi: 10.1016/j.phymed.2016.08.001. Epub 2016 Aug 10. [Article]

Drug created on February 10, 2016 16:40 / Updated on May 15, 2021 12:14