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Table 2 All published research on endometriosis and anti-inflammatory drugs done in animal models was found by searching PubMed database and the corresponding clinical trials until January 2019

From: Endometriosis: current challenges in modeling a multifactorial disease of unknown etiology

Author, year

Main drug

Drug effect

Animal model (n)

Conclusion

Clinical Trial using the same drug (ClinicalTrials.gov Identifier)

ClinicalTrial status

New endometriosis research advance

Saltan et al. (2016) [146]

Viburnum opulus

Antimicrobial, antioxidant, hepatoprotective, hypogly-cemic, antinociceptive and anti-inflammatory

Rat (30)

Endometrioctic volume reduced; Peritoneal TNF-α, VEGF and IL-6 concentration reduced

The Efficacy of Viburnum Opulus 3X in the Treatment of Primary Dysmenorrhea (NCT02467543)

Completed

Endometriosis was an exclusion criteria

Bostanci et al. (2016) [127])

Aloe Vera

Antioxidant

Rat (24)

Endometrioctic volume reduced; Peritoneal fluid antioxidant levels raised

43 trials using Aloe Vera, none using it to treat endometriosis

Zhou et al. (2012) [152]

Salvia miltiorrhiza Bunge

Anti-inflammatory, antioxidant

Rat (40)

Reduced levels of CA-125, TNF-α and IL-18. Increased levels of Il-13

2 trials with Salvia miltiorrhiza Bunge, one for Polycystic Ovary Syndrome and the other for Pulmonary conditions. None for endometriosis

Neto et al. (2011) [142]

Uncariatomentosa

Anti-inflammatory, immunomodulatory, pro-apoptotic, anti- oxidant and contraceptive

Rat (40)

Contraception

Phase II Clinical Trial of UncariaTomentosa (Cat´s Claw) in Patients With Advanced Solid Tumors (NCT02045719)

Unknown

Not associated with endometriosis

Sun et al. (2011) [149]

FubaoDangguiJiao

Abortion prevention and regulate menstruation

Rat (40)

Endometrioctic volume reduced

No clinicaltrials

Neto et al. (2011) [143]

Uncariatomentosa

Anti-inflammatory, immunomodulatory, pro-apoptotic, anti- oxidant and contraceptive

Rat (25)

Endometrioctic volume reduced

Phase II Clinical Trial of UncariaTomentosa (Cat´s Claw) in Patients With Advanced Solid Tumors (NCT02045719)

Unknown

Not associated with endometriosis

Qu et al. (2005) [145]

Yiweining

Anti-inflammatory

Rat (50)

Reduced serum levels of TNF-α, IL-6, and IL-8

Comparative study on the efficacy of Yiweining and Gestrinone for post-operational treatment of stage III endometriosis

Completed

Yiweining suppressed

post-operational relapse and dissemination of

endometriosis III

Xiao et al. (2002) [151]

Tripterygium Wilfordiipolyglycoside

Anti-inflammatory, immune modulation, antiproliferative, and proapoptotic

Rabbit (22)

Endometriotic volume and antiendometrial antibody reduced; serum FSH and LH levels decreased

6 clinical trials found on Pubmed. Noneendometriosisrelated

Its clinical use is limited duo its severe toxicity

Chen et al. (2010) [128])

15-epi-lipoxin A4

Anti-inflammatory

Mouse (45)

Supression of lesion growth

14 trials, none using for endometriosis research

Machado et al. (2010) [139]

cyclooxygenase-2 inhibitor

Inhibitor of the enzyme responsible for the production of prostaglandins which are one of the responsibles for inflammation

Rat (20)

Supression of lesion growth

682 trials, none using cyclooxygenase-2 inhibitor to treat endometriosis

Nenicu et al. (2017) [141]

1-Telmisartan and 2-parecoxib (cyclooxygenase-2 inhibitor)

1-Anti-hypertensive; 2-Inhibitor of the enzyme responsible for the production of prostaglandins which are one of the responsibles for inflammation

Mouse (42)

Supression of lesion formation and growth

282 and 47 trials, none using Telmisartan nor parecoxib to treat endometriosis respectively

Jana et al. (2012) [133])

Curcumin

Anti-oxidant and anti-inflammatory

Mouse (48)

Supression of lesion growth

Curcumin Supplementation for Gynecological Diseases (NCT03016039)

Not yet recruting

Curcumin was used to trattubo ovarian abcess, endometritis, wound infection.

Matsuzaki et al. (2004) [140]

cyclooxygenase-2 inhibitor

Inhibitor of the enzyme responsible for the production of prostaglandins which are one of the responsibles for inflammation

Rat (74)

Supression of lesion growth

682 trials, none using cyclooxygenase-2 inhibitor to treat endometriosis

Laux-Biehlmann et al. (2016) [138]

1-celecoxib (cyclooxygenase-2 inhibitor); 2-antinociceptive (Nav1.8 blocker A-803467)

1-Inhibitor of the enzyme responsible for the production of prostaglandins which are one of the responsibles for inflammation; 2-induce analgesia in inflammatory pain models

Mouse (number of animals was not described)

1-Decrease in percentage time in the standing position, associated with pain.

1. 496 trials using celecoxib, none for endometriosis; 2- 55 trials for antinociceptive none with endometriosis; 2-1 study using sodium channel blocker but not endometriosis related

Elmali et al. (2002) [130])

Caffeic acid phenethyl ester

Anti-inflammatory

Rat (30)

Decrease in osxidative stress parameters

1 clinical trial (NCT02744703) but not endometriosis related

Barretto et al. (2016) [125])

Acetylsalicylic acid

Cytolytic and antineoplastic

Rabbit (40)

Partial supression of lesion growth

1754 trails, none for endometriosis treatment

Abbas et al. (2013) [123])

β-Caryophyllene

Anti-inflammatory

Rat (27)

Supression of lesion growth without interfering with fertility

1 trial (NCT03152578) but not endometriosis related

Kizilay et al. (2017) [136]

1- Curcumin; 2-Deferoxamine

1-Anti-oxidant and anti-inflammatory; 2-Iron-chelating

Rat (30)

Supression of lesion growth

58 trials using Deferoxamine, but none for endometriosis treatment

Kiykac Altinbas et al. (2015) [135])

Montelukast

Anti-inflammatory

Rat (33)

Supression of lesion growth

287 trails using Montelukast (also searched for Singulair and MK 0476), but none for endometriosis research

Bayoglu Tekin et al. (2015) [126])

Resveratrol

Anti-angiogenic, antioxidant, anti-inflammatory

Rat (40)

Reduction on Anti-angiogenic, antioxidant, anti-inflammatory parameters

Resveratrol for Pain Due to Endometriosis (ResvEndo) (NCT02475564)

Completed (phase 4)

No difference between groups regarding pain and serum CA125 and Prolactin Levels reduction after 42 days of medication. 22 patients per group.

Hull et al. (2005) [132]

Nimesulide (COX-2 inhibitor)

Anti-angiogenic, antioxidant, anti-inflammatory

Mouse (30)

No supression of lesion growth

17 trails, none for endometriosis treatment

Efstathiou et al. (2005) [129])

1-Aspirin; 2-Celecoxib; 3-Ibuprofen; 4-Indomethacin; 5-Naproxen; 6-Sulindac; 7-Rofecoxib

Anti-angiogenic, antioxidant, anti-inflammatory

Mouse (105)

Celecoxib and indomethacin were most efficacious to supress lesion growth

and aspirin had no effect

Ibuprofen is only used in 2 clinical trials but as rescue medication, not for testing (NCT02437175; NCT01942122)

Takai et al. (2013) [150]

Parthenolide

Anti-cancer and anti-inflammatory

Mouse (30)

Inhibited endometriosis like lesion formation

4 trials, none for endometriosis propose

Kurt et al. (2015) [137]

Colchicine

Anti-inflammatory

Rat (16)

Supression of lesion formation and growth

127 trials, none to study endometriosis

Güney et al. (2008) [131]

Melatonin

Antioxidant and anti-inflammatory

Rat (25)

Supression of lesion formation and growth

441 trials using Melatonin, none using it to treat endometriosis

Kilico et al. (2014) [134])

Dexketoprofen trometamol (Cyclooxygenase-2 enzyme inhibitor)

Inhibitor of the enzyme responsible for the production of prostaglandins which are one of the responsibles for inflammation

Rat (60)

Supression of lesion formation and growth

18 trials using Dexketoprofen trometamol

(also searched as Enantyum), none to treat endometriosis

Rudzitis-Auth et al. (2013) [65]

Resveratrol

Anti-angiogenic, antioxidant, anti-inflammatory

Mouse (20)

Suppression of new microvessels in lesions

Resveratrol for Pain Due to Endometriosis (ResvEndo) (NCT02475564)

Completed (phase 4)

No difference between groups regarding pain and serum CA125 and Prolactin Levels reduction after 42 days of medication. 22 patients per group.

Agostinis et al. 2015 [124])

1- N-acetyl cysteine; 2-alpha-lipoic acid; 3- bromelain

Antioxidant, anti-inflammatory

Mouse (16)

Supression of lesion formation and growth

No endometriosis related clinical trial with neither drug

Soylu Karapinar et al. (2017) [148]

Dexpanthenol

Antioxidant, anti-inflammatory

Rat (20)

Supression of lesion growth

26 trials using Dexpanthenol (or Panthenol and Bepanthen), but nnone for endometriosis treatment

Siqueira et al. (2011) [147]

Acetylsalicylic acid

Cytolytic and antineoplastic

Rabbit (40)

Supression of lesion growth

1754 trails, none for endometriosis treatment

Olivares et al. (2011) [144]

Celecoxib (Cyclooxygenase-2 enzyme inhibitor) and rosiglitazone

Anti-angiogenic, antioxidant, anti-inflammatory

Mouse (48)

Supression of lesion formation and growth

1-Use of Rosiglitazone in the Treatment of Endometriosis (NCT00115661); 2-ffect of Rosiglitazone on Peritoneal Cytokines in Women With Endometriosis (NCT00121953)

1-Terminated; 2-Withdrawn