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. 2022 Apr 11:10:849441.
doi: 10.3389/fbioe.2022.849441. eCollection 2022.

Synthesis, Characterization, and In V ivo Toxicological Evaluation of Copper (II) Oxide Containing Herbometallic Siddha Nanocomplex "Thamira Parpam"

Parameswari Royapuram Parthasarathy  1   2 , Verasundaram M Manikandamathavan  3   4 , Chandranayagam Chandronitha  2 , Hannah R Vasanthi  2   5 , Vasanth Kumar Mohan  2 , Venkataramanan Vijayakumar  2 , Rajeshkumar Shanmugam  1 , Saravanan Sekaran  1 , Balachandran Unni Nair  3 , Duraipandian Chamundeeswari  2 , Sadras Panchatcharam Thyagarajan  2   6
Affiliations

Synthesis, Characterization, and In V ivo Toxicological Evaluation of Copper (II) Oxide Containing Herbometallic Siddha Nanocomplex "Thamira Parpam"

Parameswari Royapuram Parthasarathy et al. Front Bioeng Biotechnol. .

Abstract

"Thamira parpam" (TP), a copper-based herbometallic oxide (copper (II) oxide) nanodrug has been used in Siddha medicine for centuries because of its anti-ulcerogenic property. However, the physicochemical properties and in vivo toxicity of TP still remain elusive. Rigorous clinical translation requires deciphering these vital properties. We have synthesized TP following a gold standard protocol in the traditional Siddha methodology. We assessed the size, phase, elemental constituents, and thermal stability of TP by SEM and TEM, XRD, EPR, and EDAX analyses, respectively. The results depicted the conversion of metallic copper into copper (II) oxide in the final stages of TP preparation and exhibited nanodimensions ranging between 10 and 50 nm. The XPS spectra revealed the presence of oxygen-deficient state and a carbonaceous coating was found on the surface of TP using TEM analysis. In vivo safety was studied in rat toxicity models by adopting OECD guidelines. Body weight changes, feed, and water intake were unaltered upon TP administration. Hematological, biochemical profiling, and histopathological findings also suggested its nontoxic nature with no abnormalities in major organs and its functions. Interestingly, we found that the metal toxicity could have been subdued because of the carbonaceous coating around the nanoparticle copper (II) oxide, confirming that the drug is safe at a low dose. Overall, our study has enlightened the safety of TP supporting the use of Siddha formulations.

Keywords: Siddha; Thamira parpam; copper oxide; herbometallic; nanocomplex; toxicity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Photoemission electron (XPS) spectra of different stages Thamira parpam prepared using the traditional ancient method, showing peak positions of the Cu2p3/2 and Cu2p1/2 peak of CuO (A) Stage-1 TP; (B) Stage-5 (C) Stage-15 TP (D) Stage-25 TP.
FIGURE 2
FIGURE 2
Thermogravimetric analysis (TGA) of different stages of Thamira parpam prepared by the traditional ancient method (A) Stage-1 TP; (B) Stage-5 (C) Stage-10 TP (D) Stage-25 TP.
FIGURE 3
FIGURE 3
Room temperature electron paramagnetic resonance (EPR) spectra of various stages of Thamira parpam prepared by the traditional ancient method in comparison to the laboratory method of TP preparation. (A) Stage-1 TP; (B) Stage-5 (C) Stage-10 TP (D) Stage-15 TP; (E) Stage-25 TP.
FIGURE 4
FIGURE 4
Low-temperature (77 K) electron paramagnetic resonance (EPR) spectra of various stages Thamira parpam prepared by the traditional ancient method in comparison to the laboratory method of TP preparation. (A) Stage-1 TP; (B) Stage-5 (C) Stage-10 TP (D) Stage-15 TP; (E) Stage-25 TP; (F) CuO (G) Alangium salviifolium; (H) Aristolochia bracteata.
FIGURE 5
FIGURE 5
X-ray diffraction pattern (XRD) of various stages of Thamira parpam prepared by the traditional ancient method in comparison to the laboratory method of TP preparation. (A) Stage-1 TP; (B) Stage-5 (C) Stage-10 TP (D) Stage-15 TP; (E) Stage-25 TP; (F) CuO; (G) Aristolochia bracteolata; (H) Alangium salviifolium.
FIGURE 6
FIGURE 6
Scanning electron microscopic (SEM) images of various stages Thamira parpam prepared using the traditional ancient method.
FIGURE 7
FIGURE 7
Energy dispersive X-ray analysis (EDAX) of various stages of Thamira parpam prepared using the traditional ancient method showing presence different metals and trace elements.
FIGURE 8
FIGURE 8
Transmission electron microscopic (TEM) photograph of Thamira parpam particles obtained at various stages of preparation using the traditional ancient method. Scale bar indicates 200 nm.
FIGURE 9
FIGURE 9
Weekly body weight changes in normal, vehicle, and 28 repeated oral dose of Thamira parpam–treated male SD rats.
FIGURE 10
FIGURE 10
Weekly body weight changes in normal, vehicle, and 28 repeated oral dose of Thamira parpam–treated female SD rats.
FIGURE 11
FIGURE 11
Histopathological analysis of the liver showing no normal hepatocytes in control, vehicle, and low-dose TP-treated groups of both sexes. Mild portal inflammation observed in the mid-and high-dose TP-treated groups of male and female rats. Histopathological analysis of kidney tissues showed normal architecture of nephrons in the male and female SD rats after 28 days treatment of Thamira parpam.
FIGURE 12
FIGURE 12
Histopathological analysis of heart and brain tissues showing no abnormalities in the male and female SD rats after 28 days treatment of Thamira Parpam.
FIGURE 13
FIGURE 13
Histopathological analysis of lung and spleen tissue showing no abnormalities in the male and female SD rats after 28-day treatment of Thamira Parpam.
FIGURE 14
FIGURE 14
Histopathological analysis of stomach and adrenals showing no ulceration and abnormalities, respectively, in the male and female SD rats after 28-day treatment of Thamira parpam.
FIGURE 15
FIGURE 15
Histopathological analysis of sex organs showing normal architecture in the male and female SD rats after 28-day treatment of Thamira Parpam.
FIGURE 16
FIGURE 16
Illustration of stepwise formation of CuO involved in Thamira parpam preparation using the traditional ancient method.
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