Friday, May 19, 2017



Inflammatory Bowel Disease and Plant Medicines

A variety of plants, plant extracts,  and complex herbal formulas have  been studied in the treatment of IBD.  Central to the problem of studying this condition  is the lack of understanding about the cause.  Bowel inflammation is believed to involve the following: 1
  • ·         multiple genetic variations
  • ·         alterations in the composition of the intestinal microbiota
  • ·         changes in the surrounding environment
  • ·         overreactivity of the intestinal mucosal immune response

Herbal treatments have been identified based on ancient traditional treatments for chronic diarrhea, vomiting and other GI complaints, while more scientifically based testing has been done based on the content of anti-inflammatory compounds contained in plants.
Experimental animal studies have indicated that a variety of herbs and herbal formulas may quell gut mucosal inflammation. These are established models for the human diseases known as IBD, irritable bowel disease, ulcerative colitis, and Crohn's disease.   Most recently, cannabidiol from the hemp plant has been shown to suppress mucosal inflammation as well as hypermotility.2  A very small sampling of other plants shown in recent experimental animal studies  to have benefit include:
  • ·         Zanthoxylum myriacanthum var. pubescens 3
  • ·         A formula of Quebracho, Conker tree and M. balsamea Willd extracts 4
  • ·         Zataria multiflora Boiss 5
  • ·         Daucus carota (carrot)  6
  • ·         Boswellia serrata (conflicting results) 7,8
  • ·         Zingiber officinale (ginger)  9
  • ·         Cordia dichotoma 10
  • ·         Patrinia scabiosaefolia 11
  • ·         Vitex negundo 12
  • ·         Pistacia lentiscus 13
  • ·         Mastic 14,15,16
  • ·         Plantago ovata (psyllium) 17

Human clinical trials are naturally fewer, and there were virtually no clinical trials found in dogs and cats at the time of this review.  A systematic review 1 from 2015 highlighted the following herbs.  In all cases where adverse effects of treatment were tracked,  herbs were deemed very safe.

  • ·         Aloe vera (1 trial) - significant maintenance of remission as compared to placebo
  • ·         Andrographis paniculata (1 trial) - clinical efficancy similar to mesalamine though recurrence rate was higher
  • ·         Artemisia absinthum (2 trials) significant improvement over placebo in 1 trial but not anotherj smaller trial
  • ·         Boswellia serrata (3 trials) - treatment efficacy similar to sulfasalazine in 2 trials but not different  from  placebo in a third trial
  • ·         Cannabis sativa (THC extract, 2 trials, one not controlled)  - significantly better results over  placebo 
  • ·         Curcuma longa (turmeric, 3 trials, only 1 controlled) - reduced clinical signs and relapses as compared to placebo group.
A modern Chinese herbal formula significantly improved symptoms of irritable bowel syndrome in a randomized controlled trial in human patients 18. This trial compared patients given placebo, individualized Chinese herbal prescriptions, and standard formula. Initially, both treatment groups improved significantly compared to the placebo group; at follow-up 14 weeks later, only those receiving individualized prescriptions maintained improvement.
Standard Chinese herbal formula in Bensoussan trial
Dang Shen            Codonopsis pilosulae               7gm
Huo Xiang             Agastaches seu pogostemi      4.5gm
Fang Feng            Ledebouriella sesiloidis            3gm
Yi Yi Ren              Coicis lacryma-jobi                      7gm
Chai Hu                 Bupleurum Chinense                4.5gm
Yin Chen               Artemisia capillaris                    13gm
Bai zhu                 Atractylodes macrocephalae    9gm
Hou Po                 Magnolia officinalis                    4.5gm
Chen Pi                 Citrus reticulata                          3gm
Pao Jiang             Zingiber officinalis                     4.5gm
Qin Pi                   Fraxinus rhynchophylla             4.5gm
Fu Ling                 Poria cocos                                 4.5gm
Bai Zhi                  Angelica daihurica                    2gm
Che Qian Zi           Plantago asiatica                     4.5gm
Huang Bai             Phellodendron amurense      4.5gm
Zhi Gan Cao          Glycyrrhiza uralensis             4.5gm
Bai Shao               Paeonia lactiflora                     3gm
Mu Xiang              Aucklandia lappa                     3gm
Huang Lian            Coptis sinensis                       3gm

Wu Wei Zi             Schisandra chinensis              7gm

How might herbal medicines work to improve the clinical signs of, or even resolve, IBD?  There are a variety of potential active compound classes contained in herbs, including proteins, carbohydrates, lipids, alkaloids, glycosides, flavonoids, saponins, terpenoids, tannins and essential oils. Importantly to the practice of herbal medicine, it may be the combination of components that is most effective as opposed the singular effect of one compound.  Herbal medicines may exert anti-inflammatory, antiphlogistic, astringent, and mucosal protective effects, and may also alter the microbiome.  Botanical medicines have also been used in IBD for their psychological effects, as the pain secondary to inflammation of the bowel may alter circulation and other functions of the gut.19

Veterinarians who use integrative therapies will choose from a variety of approaches to treat this potentially deadly disease.  A change in diet is a reasonable first step, and herbal therapies often come next, sometimes along with acupuncture. Many veterinary herbalists are consulted after conventional therapies including steroids  (prednisone, budesonide) or stronger immunesuppressive therapies (cyclosporine, azathioprine, chlorambucil and even mycophenylate, leflunomide, etc ) are already on board and see an improvement when natural therapies are instituted. Patients can die of this disease, and herbal therapies are a reasonable addition at any stage in order to mitigate side effects and perhaps increase the chance of a remission.

References

1 Algieri F, Rodriguez-Nogales A, Rodriguez-Cabezas ME, Risco S, Ocete MA, Galvez J..  Botanical Drugs as an Emerging Strategy in Inflammatory Bowel Disease: A Review. Mediators Inflamm. 2015;2015:179616. doi: 10.1155/2015/179616. Epub 2015 Oct 20.

2 Pagano E, Capasso R, Piscitelli F, Romano B, Parisi OA, Finizio S, Lauritano A, Marzo VD, Izzo AA, Borrelli F. An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse.  Front Pharmacol. 2016 Oct 4;7:341.

3 Ji KL, Gan XQ, Xu YK, Li XF, Guo J, Dahab MM, Zhang P.  Protective effect of the essential oil of Zanthoxylum myriacanthum var. pubescens against dextran sulfate sodium-induced intestinal inflammation in mice.Phytomedicine. 2016 Aug 15;23(9):883-90

4 Brown K, Scott-Hoy B, Jennings LW.  Response of irritable bowel syndrome with constipation patients administered a combined quebracho/conker tree/M. balsamea Willd extract.  World J Gastrointest Pharmacol Ther. 2016 Aug 6;7(3):463-8. doi: 10.4292/wjgpt.v7.i3.463.

5 Nakhai LA, Mohammadirad A, Yasa N, Minaie B, Nikfar S, Ghazanfari G, Zamani MJ, Dehghan G, Jamshidi H, Boushehri VS, Khorasani R, Abdollahi M.. Benefits of Zataria multiflora Boiss in Experimental Model of Mouse Inflammatory Bowel Disease.  eCAM 2007;4(1)43–50 doi:10.1093/ecam/nel051

6 Patil MVK , Kandhare AD,  Bhise SD.  Anti-Inflammatory Effect Of Daucus Carota Root On Experimental Colitis In Rats. Int J Pharm Pharm Sci, Vol 4, Issue 1, 337-343

7 Madisch, A.; Miehlke, S.; Eichele, O.; Mrwa, J.; Bethke, B.; Kuhlisch, E.; Bästlein, E.; Wilhelms, G.; Morgner, A.; Wigginghaus, B. & Stolte, M. (2007). Boswellia serrata
extract for the treatment of collagenous colitis. A double-blind, randomized,  placebo-controlled, multicenter trial. International journal of colorectal disease, Vol.22,
No.12 (December 2007), pp.1445-14451.

8 Kiela, PR.; Midura, AJ.; Kuscuoglu, N.; Jolad, SD.; Sólyom, AM.; Besselsen, DG.; Timmermann, BN. & Ghishan, FK. (2005). Effects of Boswellia serrata in mouse models of chemically induced colitis. American journal of physiology. Gastrointestinal and liver physiology, Vol. 288, No.4 (April 2005), pp. G798-808. ISSN 0193-1857 

9 El-Abhar, HS.; Hammad, LN. & Gawad, HS. (2008). Modulating effect of ginger extract on rats with ulcerative colitis. Journal of ethnopharmacology, Vol.118, No.3 (August 2008), pp. 367-372. ISSN 0378-8741

10 Ganjare, AB.; Nirmal, SA.; Rub, RA.; Patil, AN. & Pattan, SR. (2011). Use of Cordia dichotoma
bark in the treatment of ulcerative colitis. Pharmaceutical biology, Vol.49, No.8 (August 2011), pp. 850-855. ISSN 1388-0209

11 Cho, EJ.; Shin, JS.; Noh, YS.; Cho, YW.; Hong, SJ.; Park, JH.; Lee, JY.; Lee, JY. & Lee, KT. (2011). Anti-inflammatory effects of methanol extract of Patrinia scabiosaefolia in mice with ulcerative colitis. Journal of ethnopharmacology, Vol.136, No.3 (July 2011), pp. 428-435. ISSN 0378-8741

12  Zaware, BB.; Nirmal, SA.; Baheti, DG.; Patil, AN. & Mandal, SC. (2011). Potential of Vitex negundo roots in the treatment of ulcerative colitis in mice. Pharmaceutical biology, Vol.49, No.8 (August 2011), pp. 874-878. ISSN 1388-0209

13 Kim, HJ. & Neophytou, C. (2009). Natural anti-inflammatory 13 compounds for the management and adjuvant therapy of inflammatory bowel disease and its drug delivery system. Archives of pharmacal research, Vol.32, No.7 (July 2009), pp. 997- 1004. ISSN 0253-6269

14 Kaliora, AC.; Stathopoulou, MG.; Triantafillidis, JK.; Dedoussis, GV. & Andrikopoulos, NK. (2007). Chios mastic treatment of patients with active Crohn's disease. World journal of gastroenterology, Vol.13, No.5 (February 2007), pp.748-753. ISSN 1007-9327

15 Kaliora, AC.; Stathopoulou, MG.; Triantafillidis, JK.; Dedoussis, GV. & Andrikopoulos NK. (2007). Alterations in the function of circulating mononuclear cells derived from
patients with Crohn's disease treated with mastic. World journal of gastroenterology, Vol.13, No.45 (December 2007), pp. 6031-6036. ISSN 1007-9327

16 Al-Habbal, MJ.; Al-Habbal, Z. & Huwez, FU. (1984). A double-blind controlled clinical trial
of mastic and placebo in the treatment of duodenal ulcer. Clinical and experimental pharmacology & physiology, Vol.11, No.5 (September 1984), pp. 541-544. ISSN 0305- 1870

17 Rodríguez-Cabezas, ME.; Gálvez, J.; Camuesco, D.; Lorente, MD.; Concha A,; MartinezAugustin, O.; Redondo, L. & Zarzuelo, A. (2003). Intestinal anti-inflammatoryactivity of dietary fiber (Plantago ovata seeds) in HLA-B27 transgenic rats. Clinicalnutrition, Vol.22, No. 5 (October 2003), pp. 463-471. ISSN 0261-5614

18 Bensoussan A; Talley NJ; Hing M; Menzies R; Guo A; Ngu M, 1998. Treatment of irritable bowel syndrome with Chinese herbal medicine: a randomized controlled trial. JAMA 11;280(18):1585-1589.

19  Lauche R, Cramer H, Klose P, Kraft K, Dobos GJ, Langhorst J. Herbal medicines for the treatment of inflammatory bowel disease. Cochrane Database of Systematic Reviews 2014, Issue 7. Art. No.: CD011223. DOI: 10.1002/14651858.CD01122


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