Balkrishna Acharya, Sharma Deepika, Sharma Rohit K, Bhattacharya Kunal, Varshney Anurag
Drug Discovery and Development Division, Patanjali Research Institute, Haridwar, Uttarakhand249405, India.
Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Roorkee-Haridwar Road, Haridwar, Uttarakhand249405, India.
ACS Omega. 2023 Jan 9;8(3):2942-2952. doi: 10.1021/acsomega.2c05391. eCollection 2023 Jan 24.
Jasada bhasma (JB) is a zinc oxide-based Indian traditional Ayurveda-based herbo-metallic nanoparticle used for the treatment of zinc (Zn) deficiency and autoimmune and inflammatory disorders. JB is made by following the Ayurveda-based guidelines using zinc oxide (ZnO) as a raw material and going through 17 cycles of the high-temperature incineration and trituration process known as "Ma̅raṇa" in the presence of herbal decoctions prepared from the leaves of and gel. These cycles improve the purity of the parent material and transform its physicochemical properties, converting it into nanoparticles. However, there still exists a knowledge gap regarding the role of incineration in the physicochemical transformation of the Zn raw material into JB nanoparticles and the biological interaction of the final product. In the present study, the JB samples obtained during different Ma̅raṇa cycles were carefully studied for their physicochemical transformation using analytical methods such as powdered X-ray diffraction (XRD), small-angle X-ray scattering (SAXS), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy, Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, and dynamic light scattering (DLS). According to the XRD results, the Zn and oxygen molecules in hexagonal ZnO wurtzite crystals gradually realigned as a result of repeated heat treatments that caused lattice tension and crystal size reduction from 53.14 to 42.40 nm. A morphological transition from 1.5 μm rod shape to 31 nm in the JB particles can be seen using FESEM and SAXS analyses. The existence of 10 nm-sized nanoparticles in the finished product was confirmed by HRTEM. The presence of ZnO was confirmed in all samples by FTIR and Raman spectroscopies. Cell viability analysis showed an inhibitory concentration 50% of >1000 μg/mL for JB nanoparticles, revealing no adverse effects in human colon Caco-2 cells. A dose-dependent uptake and intracellular accumulation of JB nanoparticles were observed in Caco-2 cells using inductively coupled plasma-based mass spectroscopy (ICP-MS). Bioavailability of Zn ions (6% w/w) through JB dissolution in acidic pH 4.0 was observed, representing the stomach and intracellular lysosomal physiological conditions. Therefore, the study showed that the repeated incineration cycles produced biocompatible JB nanoparticles through the physicochemical transformation at molecular levels capable of delivering bioavailable Zn ions under physiological conditions. In conclusion, the medicinal properties of JB nanoparticles described in Ayurveda were found to originate from their small size and dissolution properties, formed through the classical incineration-based synthesis process.
贾萨达药灰（JB）是一种基于氧化锌的、源自印度传统阿育吠陀医学的草药金属纳米颗粒，用于治疗锌（Zn）缺乏症以及自身免疫性和炎症性疾病。JB是按照阿育吠陀医学的指导方针，以氧化锌（ZnO）为原料，在由树叶和凝胶制备的草药煎剂存在的情况下，经过17个高温焚烧和研磨过程（在阿育吠陀医学中称为“玛拉纳”）制成的。这些循环提高了母体材料的纯度并改变了其物理化学性质，将其转化为纳米颗粒。然而，关于焚烧在将锌原料物理化学转化为JB纳米颗粒过程中的作用以及最终产品的生物相互作用，仍然存在知识空白。在本研究中，使用粉末X射线衍射（XRD）、小角X射线散射（SAXS）、场发射扫描电子显微镜（FESEM）、能量色散X射线光谱、傅里叶变换红外（FTIR）光谱、拉曼光谱和动态光散射（DLS）等分析方法，对在不同玛拉纳循环中获得的JB样品进行了仔细研究，以探究其物理化学转化情况。根据XRD结果，六方纤锌矿晶体中的锌和氧分子由于反复热处理而逐渐重新排列，这导致晶格张力和晶体尺寸从53.14纳米减小到42.40纳米。通过FESEM和SAXS分析可以看到，JB颗粒的形态从1.5微米的棒状转变为31纳米。高分辨率透射电子显微镜（HRTEM）证实了成品中存在10纳米大小的纳米颗粒。FTIR和拉曼光谱在所有样品中均证实了氧化锌的存在。细胞活力分析表明，JB纳米颗粒的半数抑制浓度>1000微克/毫升，表明对人结肠Caco-2细胞没有不良影响。使用基于电感耦合等离子体质谱（ICP-MS）在Caco-2细胞中观察到JB纳米颗粒呈剂量依赖性摄取和细胞内积累。观察到在酸性pH 4.0条件下，通过JB溶解可获得锌离子的生物利用度（6% w/w），这代表了胃和细胞内溶酶体的生理条件。因此，该研究表明，反复的焚烧循环通过分子水平的物理化学转化产生了具有生物相容性的JB纳米颗粒，这些纳米颗粒能够在生理条件下递送具有生物利用度的锌离子。总之，发现阿育吠陀医学中描述的JB纳米颗粒的药用特性源于其小尺寸和溶解特性，这些特性是通过基于经典焚烧的合成过程形成的。
