**4. Naturalness and herbal processing**

The preparation of herbal medicines from medicinal plants requires processes such as boiling, roasting, squeezing, and soaking [7, 57]. This is believed to mitigate exaggerated pharmacological actions, alleviate side effects, modify energy properties, mask disagreeable odors, or prolong the shelf life of crude herbs [58]. Herbal processing has been leveraged most of the times as detoxifying processes important for those herbs that are known to contain toxic or undesirable chemical components [59]. For example, steaming and frying may degrade heat-sensitive toxic, while fermentation and aging may result in enzymatic degradation of the toxic ingredients. Despite these positive implications of processing, such practices may also uncover a type of metabolite-deficiency-induced toxicity since the pharmacological potencies of herbal medicinal preparations had been touted as one subserved by synergistic interactions of disparate constituents in an extract [60, 61]. Adjuvants are also often added to enhance therapeutic effects or minimize drug toxicity, thereby broadening the spectrum of clinical application of the processed drugs. Commonly used adjuvants include vinegar, honey, wine, brine, ginger juice,

bran, and rice [58, 62]. For example, according to Li et al. [63] approximately 19.4% adverse events, associated with traditional Chinese medicine use between 1949 and 2008 in China, are reported to be ascribable to improper processing. It is believed that adjuvants participate in chemical or physical transformation that improves pharmacological effects, or alter the pharmacokinetic behavior, to provide an enhanced therapeutic effect or counteract drug toxicity [58]. Therefore, concoction, decoction, infusion, and homogenization, among others, are processes that can alter the natural constituents of medicinal plants and thereby introduce a twist in this concept of "natural."
