PMID- 38521924
OWN - NLM
STAT- MEDLINE
DCOM- 20240325
LR  - 20240325
IS  - 2662-7671 (Electronic)
IS  - 2662-7671 (Linking)
VI  - 24
IP  - 1
DP  - 2024 Mar 23
TI  - An in vitro study elucidating the synergistic effects of aqueous cinnamon extract 
      and an anti-TNF-alpha biotherapeutic: implications for a complementary and 
      alternative therapy for non-responders.
PG  - 131
LID - 10.1186/s12906-024-04438-w [doi]
LID - 131
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a critical pro-inflammatory 
      cytokine, and its abnormal production is associated with several immune mediated 
      inflammatory diseases (IMID). Biological anti-TNF-alpha therapy includes treatment 
      with monoclonal antibodies such as infliximab which have proven successful and 
      are well-tolerated in most patients. Unfortunately, some patients may not respond 
      to therapy (primary non-responders) or may lose sensitivity to the biological 
      agent over time (early and late secondary non-responders). Natural products can 
      reduce inflammation and act synergistically with small molecules or biologics, 
      although evidence remains limited. This study aimed to investigate whether 
      complementary and alternative medicine (CAM) could play a role in infliximab 
      non-responders. Reportedly, cinnamon can help manage chronic inflammatory 
      conditions owing to its anti-inflammatory properties. METHODS: We studied the 
      synergistic effects of cinnamon and infliximab in vitro using a two-step 
      approach. First, we investigated whether cinnamon and infliximab act 
      synergistically. Second, we selected conditions that supported statistically 
      significant synergy with infliximab and studied the mRNA expression of several 
      genes involved in non-response to infliximab. We used aqueous cinnamon extract 
      (aCE) from Cinnamomum cassia, Cinnamomum zeylanicum, and Cinnamomum loureiroi and 
      bioactive trans-cinnamaldehyde (TCA), cinnamic acid (CA), and eugenol to study 
      the synergy between infliximab and aCE/bioactive compounds using bioassays in 
      fibroblast (L929) and monocytic (U937) cell lines, followed by qPCR for 
      molecular-level insights. TCA, C. cassia aCE, and C. zeylanicum aCE demonstrated 
      a dose-dependent synergistic effect with infliximab. Moreover, we saw 
      differential gene expression for adhesion molecules, apoptotic factors, signaling 
      molecules, and matrix remodelers in presence and absence of aCE/bioactives. 
      RESULTS: CAM supplementation was most effective with C. cassia aCE, where a 
      synergistic effect was observed for all the tested genes specifically for MMP-1, 
      BcL-xL, Bax and JAK2, followed by TCA, which affected most of the tested genes 
      except TLR-2, MMP1, MMP3, TIMP-1, and BAX, and C. zeylanicum aCE, which did not 
      affect ICAM-1, VCAM-1, TLR-2, TLR-4, MMP1, MMP3, TIMP-1, and STAT3. CONCLUSION: 
      In conclusion, cinnamon acted synergistically with infliximab to mitigate 
      inflammation when used as an extract. Purified bioactive TCA also showed 
      synergistic activity. Thus, aCE, or cinnamon bioactive may be used as a CAM to 
      improve patients' quality of life.
CI  - (c) 2024. The Author(s).
FAU - Khedkar, Shubrata
AU  - Khedkar S
AD  - Department of Biochemistry, School of Bioengineering and Biosciences, Lovely 
      Professional University, Jalandhar, 144411, Punjab, India.
FAU - Khan, Minhaj Ahmad
AU  - Khan MA
AD  - Department of Biochemistry, School of Bioengineering and Biosciences, Lovely 
      Professional University, Jalandhar, 144411, Punjab, India. 
      minhaj.15324@lpu.co.in.
LA  - eng
PT  - Journal Article
DEP - 20240323
PL  - England
TA  - BMC Complement Med Ther
JT  - BMC complementary medicine and therapies
JID - 101761232
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - B72HH48FLU (Infliximab)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tumor Necrosis Factor Inhibitors)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (Plant Extracts)
SB  - IM
MH  - Humans
MH  - *Tumor Necrosis Factor-alpha
MH  - Cinnamomum zeylanicum
MH  - Infliximab/pharmacology
MH  - Matrix Metalloproteinase 1
MH  - Matrix Metalloproteinase 3
MH  - Tissue Inhibitor of Metalloproteinase-1
MH  - Tumor Necrosis Factor Inhibitors
MH  - Toll-Like Receptor 2
MH  - Quality of Life
MH  - bcl-2-Associated X Protein
MH  - *Complementary Therapies
MH  - Plant Extracts/pharmacology
MH  - Inflammation
PMC - PMC10960381
OTO - NOTNLM
OT  - Aqueous extract
OT  - CAM
OT  - Cinnamon
OT  - Inflammation
OT  - Infliximab
COIS- None declared.
EDAT- 2024/03/24 06:42
MHDA- 2024/03/25 06:42
PMCR- 2024/03/23
CRDT- 2024/03/24 00:28
PHST- 2023/08/30 00:00 [received]
PHST- 2024/03/15 00:00 [accepted]
PHST- 2024/03/25 06:42 [medline]
PHST- 2024/03/24 06:42 [pubmed]
PHST- 2024/03/24 00:28 [entrez]
PHST- 2024/03/23 00:00 [pmc-release]
AID - 10.1186/s12906-024-04438-w [pii]
AID - 4438 [pii]
AID - 10.1186/s12906-024-04438-w [doi]
PST - epublish
SO  - BMC Complement Med Ther. 2024 Mar 23;24(1):131. doi: 10.1186/s12906-024-04438-w.