Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway Cell Physiol Biochem 2017;43:540–552 - DOI:10.1159/000480527 Fig. 1. Camel milk ameliorates Adjuvant-induced arthritis in rats. (A) Effect of Camel milk administration for 21 days on paw edema in Adjuvant arthritic rats. (A) Effect of Camel milk administration for 21 days on paw edema in adjuvant arthritic rats. (B) Effect of Camel milk on Arthritic index score on day 21. (C) The impact on animal’s gait score on day 21. Parametric values are expressed as mean ± SEM (n= 6-8) for (A) while non-parametric data in (B) and (C) are expressed as medians (n=6-8). *Significant difference vs control gp at p<0.05, # Significant difference vs arthritic gp at p<0.05. AA; Adjuvant arthritis, CM; Camel milk, DF; diclofenac. © 2017 The Author(s). Published by S. Karger AG, Basel - CC BY-NC-ND 4.0

Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway Cell Physiol Biochem 2017;43:540–552 - DOI:10.1159/000480527 Fig. 2. Camel milk mitigates pouch lining histopathologic changes and exudate leukocyte infiltration in arthritic rats. (A-C) Representative photomicrographs of pouch lining harvested on day 21 and stained with H&E (magnification × 200). (a) Pouch lining of arthritic gp revealed massive recruitment of inflammatory cells (m). (B,C) Lining of Camel milk- and diclofenac-treated arthritic rats, respectively, displaying attenuated influx of leukocytes (m) and newly formed blood capillaries (hollow arrow) along with resolving regions of fibroblasts (f). (D) Leukocyte count in pouch exudate of arthritic rats. Values are expressed as mean ± SEM (n= 6-8). # Significant difference vs arthritic gp at p<0.05. AA; Adjuvant arthritis, CM; Camel milk, DF; diclofenac. © 2017 The Author(s). Published by S. Karger AG, Basel - CC BY-NC-ND 4.0

Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway Cell Physiol Biochem 2017;43:540–552 - DOI:10.1159/000480527 Fig. 3. Camel milk attenuates systemic and local inflammation in arthritic rats. (A) Levels of TNF-α in sera and exudates of arthritic rats. (B) Levels of IL-10 in sera and exudates of arthritic rats. Values are expressed as mean ± SEM (n= 6-8). *Significant difference vs control gp at p<0.05, # Significant difference vs arthritic gp at p<0.05. AA; Adjuvant arthritis, CM; Camel milk, DF; diclofenac. © 2017 The Author(s). Published by S. Karger AG, Basel - CC BY-NC-ND 4.0

Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway Cell Physiol Biochem 2017;43:540–552 - DOI:10.1159/000480527 Fig. 4. Camel milk down-regulates NF-κBp65 protein expression in pouch lining of arthritic rats. (A-C) Representative images of pouch lining of arthritic rats (magnification × 100) showing immunohistochemical staining of NF-κBp65 expression. (D) Optical density of NF-κBp65 expression in pouch lining. Values are expressed as mean ± SEM (n= 4). # Significant difference vs arthritic gp at p<0.05. AA; Adjuvant arthritis, CM; Camel milk, DF; diclofenac. © 2017 The Author(s). Published by S. Karger AG, Basel - CC BY-NC-ND 4.0

Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway Cell Physiol Biochem 2017;43:540–552 - DOI:10.1159/000480527 Fig. 5. Camel milk down-regulates COX-2 protein expression in pouch lining of arthritic rats. (A-C) Representative images of pouch lining of arthritic rats (magnification × 100) showing immunohistochemical staining of COX-2 expression. (D) Optical density of COX-2 expression in pouch lining. Values are expressed as mean ± SEM (n=4). # Significant difference vs arthritic gp at p<0.05. AA; Adjuvant arthritis, CM; Camel milk, DF; diclofenac. © 2017 The Author(s). Published by S. Karger AG, Basel - CC BY-NC-ND 4.0

Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway Cell Physiol Biochem 2017;43:540–552 - DOI:10.1159/000480527 Fig. 6. Camel milk downregulates iNOS protein expression in pouch lining of arthritic rats. (A-C) Representative images of pouch lining of arthritic rats (magnification × 100) showing immunohistochemical staining of iNOS expression. (D) Optical density of iNOS expression in pouch lining. Values are expressed as mean ± SEM (n= 4). # Significant difference vs arthritic gp at p<0.05. AA; Adjuvant arthritis, CM; Camel milk, DF; diclofenac. © 2017 The Author(s). Published by S. Karger AG, Basel - CC BY-NC-ND 4.0

Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway Cell Physiol Biochem 2017;43:540–552 - DOI:10.1159/000480527 Fig. 7. Camel milk suppresses the activation of mitogen activated protein kinase (MAPK) pathway in hind paw homogenates of arthritic rats. (A) Western blot analysis depicting the expression of phosphorylated and total protein forms of p38 MAPK, ERK1/2 and JNK1/2. Lamin B was utilized to prove equal loading of total protein lysate. (B) Relative expression of phospho-p38MAPK. (C) Relative expression of phospho-ERK1/2. (D) Relative expression of phospho-JNK1/2. The control value was set as 1.0. Data were extracted from 3 independent experiments and values were expressed as mean ± SEM.*Significant difference vs control gp at p<0.05, # Significant difference vs arthritic gp at p<0.05. AA; Adjuvant arthritis, CM; Camel milk, DF; diclofenac. © 2017 The Author(s). Published by S. Karger AG, Basel - CC BY-NC-ND 4.0

Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway Cell Physiol Biochem 2017;43:540–552 - DOI:10.1159/000480527 Fig. 8. Camel milk alleviates systemic and local oxidative stress markers in arthritic rats. The Levels of lipid peroxides expressed as MDA (A), NO (B), GSH (C) and TAC (D) were determined in sera (blood for GSH) and exudates of arthritic rats. Values are expressed as mean ± SEM (n= 6-8). *Significant difference vs control gp at p<0.05, # Significant difference vs arthritic gp at p<0.05. AA; Adjuvant arthritis, CM; Camel milk, DF; diclofenac. © 2017 The Author(s). Published by S. Karger AG, Basel - CC BY-NC-ND 4.0