Identification

Name
Sennosides
Accession Number
DB11365
Type
Small Molecule
Groups
Approved
Description

Sennosides (also known as senna glycoside or senna) is a medication used to treat constipation and empty the large intestine before surgery. The medication is taken by mouth or via the rectum. It typically begins working in minutes when given by rectum and within twelve hours when given by mouth. It is a weaker laxative than bisacodyl or castor oil. 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].

Synonyms
  • Senna
  • Senna glycosides
  • Sennoside
  • Sennosides
Product Ingredients
IngredientUNIICASInChI Key
Sennosides A and B1B5FPI42EN62211-03-4Not applicable
Product Images
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Agarol Extra Strength Chewable Laxative TabletsTablet25 mgOralNumark Laboratories, Inc.2000-08-212009-07-31Canada
Agarol With SennosidesLiquid25 mgOralNumark Laboratories, Inc.1999-06-302009-07-31Canada
AgoralLiquid8.3 mg/5mLOralNumark Brands, Inc1942-05-05Not applicableUs
Assured Natural LaxativeTablet, coated8.6 mg/1OralSpirit Pharmaceuticals LLC2016-08-122016-07-28Us
Bekunis Natures Gentle Laxative Herbal TeaExtract23 mg/1gOralRoha Arzneimittel Gmbh2011-03-21Not applicableUs
Bekunis Natures Gentle Laxative Instant TeaPowder20 mg/0.5gOralRoha Arzneimittel Gmbh2011-03-21Not applicableUs
Bekunis Natures Gentle Stimulant LaxativeTablet, sugar coated20 mg/1OralRoha Arzneimittel Gmbh2011-02-10Not applicableUs
Best Choice SennaTablet8.6 mg/1OralValu Merchandisers Company (Best Choice)2012-05-18Not applicableUs
CAREALL SennosidesTablet8.6 mg/1OralNew World Imports2016-04-18Not applicableUs
Castoria Liq 0.7mg/mlLiquid.7 mgOralThe Mentholatum Company1919-12-311997-11-27Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Bekunis DrageesSennosides (20 mg) + Sennosides (25 mg) + Sennosides (60 mg) + Bisacodyl (5 mg)TabletOralRoha Arzneimittel Gmbh1974-12-312009-07-02Canada
Bekunis DrageesSennosides (20 mg) + Sennosides (25 mg) + Sennosides (60 mg) + Bisacodyl (5 mg)TabletOralRoha Arzneimittel Gmbh1974-12-312009-07-02Canada
Bekunis DrageesSennosides (20 mg) + Sennosides (25 mg) + Sennosides (60 mg) + Bisacodyl (5 mg)TabletOralRoha Arzneimittel Gmbh1974-12-312009-07-02Canada
CAREALL Senna-S LaxativeSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)TabletOralNew World Imports2016-04-18Not applicableUs
CennlacsSennosides (726 mg) + Glycyrrhiza glabra (182 mg)PowderOralWestward Distributors1983-12-311997-05-30Canada
ColaceSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)Tablet, film coatedOralAvrio Health L.P.1957-02-08Not applicableUs
ColaceSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)Tablet, film coatedOralAvrio Health L.P.1957-02-08Not applicableUs
Colistat PlusSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)Tablet, film coatedOralAmvilab Llc2015-07-16Not applicableUs
DocQLaxSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)Tablet, film coatedOralPar Pharmaceutical2007-07-262020-05-31Us
Docusate Plus SennaSennosides A and B (8.6 min/1) + Docusate sodium (50 mg/1)Tablet, film coatedOralSafecor Health, LLC2014-09-30Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Medi-laxx Rx Stool Softener and LaxativeSennosides (8.6 mg/1) + Docusate sodium (50 mg/1)TabletOralTwo Hip Consulting, Llc2014-12-052016-04-11Us
Categories
UNII
9VK7V8762D
CAS number
Not Available
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

For the over the counter treatment of constipation [Label].

Associated Conditions
Pharmacodynamics

Senna stimulates peristalsis and increases fecal water content to increase motility of feces through the large intestine [6] [2].

Mechanism of action

Sennoside A and B, the components of senna, are metabolized by gut bacteria into the active metabolite rheinanthrone Rheinanthrone. 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 intestine. A decrease in aquaporin 3 expression likely produces the laxative effect by restricting water reabsorption by the large intestine thereby increasing fecal water content. The exact mechanism by which rheinanthrone increases COX2 expression is unknown. Rheinanthrone Rheinanthrone also stimulates peristalsis in he large intestine although the mechanism behind this effect is unknown [6]. Rhein Rhein, another active metabolite is thought to excite submucosal acetylcholinergic neurons resulting in increased chloride and prostaglandin secretion. The movement of chloride ions into the large intestine would also help to draw water into the lumen [9].

TargetActionsOrganism
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://www.drugbank.ca/drugs/DB13175)[10].

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Sennosides A and B are metabolised to sennidins A and B by gut bacteria [6]. Sennidins A and B are further metabolized to rheinanthrone Rheinanthrone by gut bacteria using beta-glucosidase [2]. Rheinanthrone Rheinanthrone is absorbed into systemic circulation where 2.6% is metabolized to rhein Rhein and sennidins A and B via oxidation [4] [7] [2]. Rheinanthrone Rheinanthrone is the major active metabolite of sennosides A and B which produces the laxative effect of the medication. Rhein Rhein is also an active metabolite known to have many protective effects [8].

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 unchanged [10].

Half life
Not Available
Clearance
Not Available
Toxicity

Senna causes increased amounts of apoptosis in the large intestine shortly after use due to upregulated p53 activity [3]. 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 cancer. 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 toxicity [5]. Tests for mutagenicity and reproductive toxicity do not indicate toxic effects.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
AgmatineThe therapeutic efficacy of Sennosides can be decreased when used in combination with Agmatine.
AlcuroniumThe therapeutic efficacy of Sennosides can be decreased when used in combination with Alcuronium.
AlfentanilThe therapeutic efficacy of Sennosides can be decreased when used in combination with Alfentanil.
AlphacetylmethadolThe therapeutic efficacy of Sennosides can be decreased when used in combination with Alphacetylmethadol.
AlphaprodineThe therapeutic efficacy of Sennosides can be decreased when used in combination with Alphaprodine.
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.
Food Interactions
Not Available

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. [PubMed:27765358]
  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. [PubMed:24412547]
  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. [PubMed:11523059]
  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. [PubMed:6117629]
  5. Mengs U: Toxic effects of sennosides in laboratory animals and in vitro. Pharmacology. 1988;36 Suppl 1:180-7. [PubMed:3368517]
  6. Hardcastle JD, Wilkins JL: The action of sennosides and related compounds on human colon and rectum. Gut. 1970 Dec;11(12):1038-42. [PubMed:4929273]
  7. de Witte P, Lemli J: Metabolism of 14C-rhein and 14C-rhein anthrone in rats. Pharmacology. 1988;36 Suppl 1:152-7. [PubMed:3368514]
  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. [PubMed:26185519]
  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. [PubMed:8234445]
  10. Senokot Tablet Product Information [Link]
External Links
Human Metabolome Database
HMDB34317
KEGG Compound
C10404
PubChem Substance
347911200
ChemSpider
65892
BindingDB
92481
ChEBI
9112
ChEMBL
CHEMBL2368547
Wikipedia
Senna_glycoside
ATC Codes
A06AB56 — Senna glycosides, combinationsA06AB06 — Senna glycosides
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
1CompletedTreatmentIleus1
2CompletedTreatmentFunctional Constipation / Gastrointestinal Disorders1
2RecruitingTreatmentDiabetic Gastroparesis1
2, 3CompletedTreatmentColonoscopy1
2, 3CompletedTreatmentOccasional Constipation1
3CompletedTreatmentChronic Constipation1
3CompletedTreatmentOccasional Constipation2
3Unknown StatusDiagnosticHemorrhage, Gastrointestinal / Refractory Anemia / Small Bowel Diseases1
4CompletedNot AvailableColonoscopy Preparation1
4CompletedTreatmentColonoscopy Preparation1
4CompletedTreatmentOpioid Induced Constipation (OIC)1
4RecruitingPreventionOccasional Constipation1
4RecruitingTreatmentOccasional Constipation / Peritoneal dialysis complication1
4SuspendedSupportive CareMalignancies / Occasional Constipation1
4TerminatedNot AvailableColonoscopy Preparation1
Not AvailableCompletedDiagnosticColorectal Cancer Screening1
Not AvailableCompletedOtherBowel preparation therapy / Colonoscopy / Colonoscopy Preparation Outcome1
Not AvailableCompletedPreventionOccasional Constipation / Palliative Care1
Not AvailableCompletedTreatmentAutistic Disorder / Encopresis1
Not AvailableCompletedTreatmentChronic Idiopathic Constipation1
Not AvailableCompletedTreatmentEnd Stage Renal Disease (ESRD) / Pruritus1
Not AvailableCompletedTreatmentOccasional Constipation1
Not AvailableNot Yet RecruitingBasic ScienceIntestinal Transit1
Not AvailableNot Yet RecruitingPreventionColostomy Stoma / Hirschprung's Disease / Ileostomy - Stoma / Inflammatory Bowel Diseases (IBD) / Intestinal Obstruction / Jejunostomy Stoma / Meconium Ileus / NEC1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral25 mg
LiquidOral25 mg
LiquidOral8.3 mg/5mL
ExtractOral23 mg/1g
PowderOral20 mg/0.5g
Tablet, sugar coatedOral20 mg/1
LiquidOral.7 mg
Tablet, chewableOral8.6 mg/1
Bar, chewableOral15 mg/1
Tablet, chewableOral15 mg/1
PillOral15 mg/1
LiquidOral
TabletOral8.6 mg
TabletOral12 mg
TabletOral175 mg
LiquidOral100 g
ExtractOral1000 mg/1g
PowderOral1000 mg/1g
TabletOral12 mg/1
Tablet, sugar coatedOral25 mg/1
PillOral25 mg/1
TabletOral15 mg
TabletOral25 mg/1
Tablet, coatedOral15 mg/1
LiquidOral8.8 mg/1mL
Tablet, coatedOral25 mg/1
CapsuleOral
TabletOral15 mg/1
CapsuleOral15 mg
PowderOral
LiquidOral10.5 mg
LiquidOral8.8 mg/5mL
Tablet, coatedOral
Capsule, gelatin coatedOral8.6 mg/1
LiquidOral415.36 mg/236mL
SyrupOral8.8 mg/5mL
TabletOral250 mg
Tablet, film coatedOral8.6 mg/1
TabletOral8.6 mg/1
TabletOral160 mg/1
Not applicableOral0.4 g
TabletOral
Tablet, film coatedOral
Tablet, coatedOral8.6 mg/1
Tablet, sugar coatedOral15 mg/1
PowderOral326 mg
SuppositoryRectal652 mg
PillOral
TabletOral17.2 mg/1
JellyOral5 mg
Capsule, gelatin coatedOral
LiquidOral1.7 mg
PowderOral3.5 g
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

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. [PubMed:27765358]

Drug created on February 10, 2016 09:40 / Updated on November 14, 2018 12:59