**4.2 Duration of treatment**

Evaluations of most of the PH for toxicological profiles are most unlikely not going to be sufficient to determine the endpoint toxicity [24]. For instance, the majority of the acute to chronic studies found in the literature were between 14 and 90 or 180 days. However, only a few studies show reversibility assessments or show species specifications [38]. Over 80–90% of the toxicological studies published showed few or no adverse drug reactions. Also, the parameters for their toxicological endpoint did not capture genotoxicity potential [39]. As with the case of CG, which supposedly should provide a maximum antioxidant function by GSH synthesis rates and concentrations as expressed by the content could act as a pro-oxidant causing oxidative damage in normal humans particularly at high dosages [28]. Such transition in chemical nature could generate pro-oxidant–antioxidant imbalance thereby produce undesirable toxins leading to oxidative stress [22, 25]. Hence, a long-term toxicological profile plus storage history has been recommended to ascertain PH safety.


#### **Table 1.**

*Shows the potential targets of PH-induced lipid peroxidation.*

#### **4.3 Lethal dose estimation**

The median lethal dose (LD50) is the statistically derived dose following the administration of any PH which is expected to produce death in 50% of the treated population [40]. The toxic effects of chemicals, food substances, pharmaceuticals, etc., have attained great significance in the 21st century [17]. Toxicity tests are mostly used to examine specific adverse events or specific endpoints in disease identifications. Toxicity testing also helps to calculate the No or Low Observed Adverse Effect Level (NOAEL/LOAEL) dose and is helpful for clinical studies [39]. However, the methods of determination of median lethal dose (LD50) may impact negatively on the information for the use of PH. Therefore exaggerated lipid peroxidation levels due to PH might be the results of poor safety methodology [23]. This however can be minimized by using several methods to ascertain the PH LD50 level. Studies have suggested that lack of expertise in this aspect of scientific investigation might influence judgment on the PH formula [24]. Inability to in-cooperate the knowledge of individual median lethal dose might create impurities in the constituent mixture. The five most commonly paraded bitters in Nigeria for type 2 diabetes are Yoyo bitters (YB), Oroki herbal mixture (OB), Ruzu Bitters (RB), Fijk flusher (FB), and Fidson Bitter (FB) respectively. Although, each of this preparation has claimed for several indications, however, scientific investigations for the mixture have reported weight trimming and blood sugar modulations (Kale et al., 2018). Since their constituents are known, their ability to act synergistically and the potential for precipitating adverse herb reaction of LPO have been ascertained [15]. These concerned mixtures have multifaceted constituents most of which have popular applications. Examples include ginseng, *Aloe vera*, *Citrus aurantifolia*, *Sorghum bicolor*, *Mangifera indica*, etc. These have yielded very important phytomedicines or bioactive components that have been confirmed by different studies, although, some exhibit overlapping effects in disease management. *Chenopodium murale* (Chenopodiaceae) has yielded analgesics, anti-inflammatory, anti-fungal, antibacterial, anti-oxidant, hypotensive, and hepatoprotective molecules. These PH administrations improved lipid parameters in diabetic rats. While hypercholesterolemia persists in diabetic rats treated with RB and FJB, RB increased LDL in treated rats [15]. Further, RB, FJB, and OB showed tendencies to elevate serum TC while RB increases LDL cholesterol in rats. This indicates the suitability of these products to produce LPO molecules as a risk factor for dyslipidemia in potential users.

#### **4.4 Manufacturer Bias**

In contrast to the general belief, medicinal plant preparations have been shown to pose serious health risks in a dose and time-dependent either alone or in combination with other agents [19, 38]. Reports have it that PH contain tightly bound bioactive compounds and have shown the possibilities of an indirect risk that can be independent of the active compound [16]. Countries are now examining national pharmacovigilance data using statistical tools to report population possible risks [24]. This is because, oftentimes, the species specification by manufacturers on PH constituents did not correlate most times with products packaging thereby altering scientific decision on toxicological evaluations [25]. The potential to generate lipid peroxidation by several PH are underestimated [14]. On the other hand, the latter creates a contrast in mind when a single compound has a toxicity level greater than the combined mixture. Additionally, erroneous claims of total cure and or weight supporting supplement some of these PH are marketed with approved consent from regulatory authorities [22]. There are also exaggerations of PH with conventional drugs which have been suggested to contribute in part to the unwanted adverse reaction of some PH [14, 20, 23]. Thus, this issue

#### *Lipid Peroxidation and the Redox Effects of Polyherbal DOI: http://dx.doi.org/10.5772/intechopen.97625*

associated with production bias has raised concern about quality control, screening methods as well as toxicity scoring which most regulatory authorities however have not been able to properly address it. Bon-santé cleanser® (BS) is a popular PH comprising of anogeissus leiocarpus (DC., family Combretaceae), *Terminalia ivorensis* (A. Chev.), massularia acuminate (G. Don,) Bullock ex Hoyle and macuna pruriens (L.,) DC (fabaceae) respectively which have been formulated into capsule. The proposed claims include androgenic, antipyretic, analgesic, and anti-inflammatory potentials. The pharmacological activities of *M. acuminata*, *T. ivorensis*, A. leiocarpus and *M. pruriens* have been adduced to be due to the presence of glycosides, dimeric antioxidants, phenolics and flavones respectively. Despite the relevance of BS in boosting the body hormones including the follicle-stimulating, luteinizing hormone and testosterone respectively, reports have implicated this BS as a potential hepatotoxicant and a commodity with pro-oxidants status. Increasing the dose of BS was associated with significantly reduced sperm motility, live-dead ratio, testis weight, and cause mild inflammation in the vital organs testis in the animals [40]. There was diminishing return as higher doses did not exert any significantly different change in the level of body hormones which could cause the negative feedback effect on the anterior pituitary [33]. Further, this PH demonstrates the potential to induce LPO of the testicular origin or promote the generation of free radicals in vivo.
