Page 95 - ITPS-7-1

INNOSC Theranostics and
Pharmacological Sciences Plants immunoactivity: In silico study

The sum of targets for the control IMiDs, Thalidomide also displayed connections to various immune pathways
(20 targets retrieved) and Lenalidomide (28 targets (Table 2), thereby shedding light on the pathways through
retrieved), totaled 48. This set of targets overlapped with which the bioactives exert their immunomodulatory effects.
the bioactives’ immune targets, resulting in a total of 90
bioactive-multiple myeloma immune gene targets. 3.7. Network-based analysis of active
phytocompounds’ immunomodulatory potential in
3.6. Network-based evaluation of the multiple myeloma
immunomodulatory mechanisms of active To delve into the network-based analysis of the systems-level
phytocompounds immunomodulatory properties of the phytocompounds
To comprehend the “multi-components, multi-target, and present within the herbal plants, a C-T network was
multi-pathway” immunomodulatory mechanisms of W. constructed (Figure 2). This network comprised 99
somnifera and A. barbadensis, a compound-target network nodes and 447 edges, achieved through associating active
was constructed. This network linked active phytochemical compounds with their corresponding multiple myeloma-
compounds to their corresponding immune targets, gene targets. The nodes included 37 active compounds, 2
which were subsequently analyzed. The compound-target control drugs, and 60 bioactive-multiple myeloma immune
network for these two herbal plants comprised 205 nodes gene targets. Targets not involved in KEGG immune
and 1338 edges, encompassing 36 active compounds pathways were excluded.
and 169 targets. Among the active phytochemical Within this network, 10 active phytochemical
compounds, their categorization was based on degrees compounds, including withanolide Q (degree =
of connectivity. Notably, withanolide Q (degree = 70), 25), hydrocortisone (degree = 24), somniferine
2,3-didehydrosomnifericin (degree = 69), steroids (degree = (degree = 22), 2,3-didehrdrosomnifericin (degree = 22),
65), hydrocortisone (degree = 63), 27-deoxywithaferin A 27-deoxywithaferin A (degree = 21), steroids (degree = 20),
(degree = 62), withaferin A (degree = 61), somniferine withaferin A (degree = 19), withanolide G (degree = 17),
(degree = 59), withanolide G (degree = 58), somniferanolide somniferanolide (degree = 17), and lenalidomide
(degree = 55), Ssominone (degree = 53), chlorogenic (degree = 16), had the most linkages with multiple
acid (degree = 47), somniwithanolide (degree = 47), myeloma-related targets (Figure 2), thereby implying their
rhein (degree = 43), gugglesterone (degree = 39), and pivotal roles as key phytocompounds responsible for the
somnifericin (degree = 39) displayed the highest number of herbal plants’ immunomodulatory efficacy against multiple
connections with the immune-related targets. This pattern myeloma. Furthermore, 40 targets displayed two or more
indicated their potential role as primary active compounds interactions with the active phytocompounds (Figure 2),
responsible for the immunomodulatory activity of W. demonstrating herbal medicines’ multi-compound, multi-
somnifera and A. barbadensis. Furthermore, more than 70 target pharmacology.
targets demonstrated interactions with two or more active
phytochemical compounds, demonstrating the multi- In the context of the bioactive-multiple myeloma’s
compound, multitarget pharmacological properties of immune (C-T) network, the hub node target genes were
these herbal plants. identified. Nodes possessing a degree larger than or equal
to twice the network’s average node degree were classified
The STRING database also identified the PPi, forming as hubs. Core nodes, in particular, have been demonstrated
a network comprising 169 nodes and 1,553 edges, with a to play an essential role in a wide variety of biological
PPi enrichment P-value of <1.0e-16 (Figure 1). This value processes . Among the multiple myeloma-associated
[39]
indicates that the interactions among these proteins exceed targets of the bioactives, several stand out as core gene
what would be expected in a randomly selected group targets with potential roles in the immunomodulatory
of proteins with equivalent size and degree distribution potential of active phytocompounds in herbal plants
from the genome. This enrichment signifies that these (Figure 3). Specifically, these include alpha serine/
proteins are interconnected beyond chance, indicating threonine protein kinase 1 (AKT1) (degree = 29), HCK
a cohesive physiological relationship among them. proto-oncogene (HCK) (degree = 27), 3-phosphoinositide-
On delving into the disease-gene association, several dependent protein kinase 1 (PDPK1) (degree = 26), Janus
immune-associated diseases were identified: autoimmune kinase 2 (JAK2) (degree = 26), proto-oncogene c-KIT
lymphoproliferative syndrome, myeloid neoplasm, (KIT) (degree = 24), matrix metallopeptidase 9 (MMP9)
combined immunodeficiency, autoimmune disease of (degree = 23), growth factor receptor bound protein 2
the musculoskeletal system, primary immunodeficiency (GRB2) (degree = 22), interleukin 2 (IL2) (degree = 21),
disease, autoimmune disease, immune system disease, and Bruton tyrosine kinase (BTK) (degree = 19), and mouse
hematopoietic system disease. A subset of these targets double minute 2 homolog (MDM2) (degree = 19).

Volume 7 Issue 1 (2024) 6 https://doi.org/10.36922/itps.1076