East African quintessential plants claimed to be used as blood purifiers, cleansers, detoxifiers and tonics: an appraisal of ethnobotanical reports and correlation with reported bioactivities

Abstract Background: Blood cleansing, purification, detoxification or strengthening is an ancient folkloric East African practice without any validated scientific underpinnings. This study was undertaken to retrieve ethnobotanical information and reported bioactivities of plants claimed to be blood purifiers, cleansers, detoxifiers and tonics in Eastern Africa and correlate their claimed use with scientific studies to find out whether there is any justification for their use in this ancient practice. Method: An elaborate review was performed in electronic databases (PubMed, Science Direct, Scopus, Springer Link, Wiley Online Library, Taylor & Francis Online, SciFinder, Google Scholar, Web of Science) and the Google search engine to retrieve information on ethnomedicinal plants used in East Africa in blood purification, detoxification, cleansing or strengthening and their investigated bioactivities related to their use in this traditional practice. Results: The search retrieved 74 plant species from 45 families distributed among 66 genera with some documented bioactivities, though, with little correlation with their traditional utilization in blood purification, cleansing, detoxification and strengthening. Some justification of the link between blood purification, cleansing, detoxification and strengthening and the use of the plants as antiplatelet aggregation, vasorelaxant, bronchodilatory, antihyperlipidaemic, cardioprotective, antiatherosclerotic and immunomodulatory agents were evident, but majorly antimicrobial activity has been investigated in most species. Thus, only 15 (20.2%) of the plant species (Allium sativum, Moringa oleifera, Olea capensis, Clausena anisata, Centella asiatica, Nasturtium officinale, Solanum nigrum, Withania somnifera, Rubus apetalus, Delonix elata, Persia americana, Aloe vera, Azadirachta indica, Echinacea angustifolia and Dioscorea bulbifera) could be directly correlated with studies pertaining to blood health. Conclusion: Medicinal plants used in blood purification, cleansing, detoxification and strengthening in East Africa play a holistic role in rejuvenation of overall human health. Few studies have examined their bioactivities pertaining to blood health. Thus, bioactivities and pharmacological activities (such as blood thinning, hypolipemic, cardioprotective, immunomodulatory, tonic and renoprotective properties) and phytochemicals of the claimed plants warrant


Background
Natural products continue to be well recognized as the source of most known therapeutically effective commercial drugs. This is due to their distinct features and their being the origin of many pharmaceutical products, including digoxin, acetylsalicylic acid, atropine, morphine and colchicine (Atanasov et al. 2021). Plants are the most widely used natural products for their supposed medicinal potential from time immemorial. They are reportedly used by more than 60% of the global population for treatment of various diseases and conditions (WHO 2019). This is evident in developing countries where there are shrinking health services, poverty and the aphorism that herbal medicines are more effective, safe, accessible, affordable and culturally acceptable (Schultz et al. 2020;Tabuti et al. 2010;Tugume et al. 2016). Therefore, increased ethnobotanical surveys and pharmacological investigations have been done for medicinal flora worldwide in the past decades.
In Africa, and particularly Eastern Africa, which is a treasure trove of medicinal plants, several plants have been reported to be used in traditional medicine. The range of diseases and conditions treated span from simple wounds, cough and fevers to complicated conditions such as cancer, snakebites and blood purification (Schultz et al. 2020;Omara et al. 2021a;Kathambi et al. 2020;Anywar et al. 2020). Blood cleansing, purification, detoxification or strengthening is an old complementary and alternative medicine practice which has involved the use of plants in many cultures. However, there are no clearly established scientific evidences which indicate the role of plants in this ancient practice (Vuuren and Frank 2020; Keville 1990;Akter et al. 2012). In the current study, ethnobotanical information and bioactivities of plants popularly claimed to be used as blood purifiers, blood cleansers, blood detoxifiers or blood tonics in Eastern Africa were explored. The bioactivities were correlated with the claimed use of the plants to discern if there is any justification for their use in this ancient practice.

Methodology
This non-systematic review retrieved scholarly information on ethnomedicinal plants claimed to be used in East Africa for blood purification, detoxification, cleansing or strengthening dated until August 2021. East Africa was taken as East African community, the region including Uganda, Kenya, Tanzania, Rwanda, Burundi and South Sudan (Omara et al. 2021b). An elaborate electronic review was performed in PubMed, Science Direct, Scopus, Springer Link, Wiley Online Library, Taylor & Francis Online, SciFinder, Google Scholar and Web of Science Core Collection. A more general search was further performed using the Google search engine to capture documents, reports, botanical databases and theses from various University repositories. This gathered all the published work (ethnobotanical books, reviews, reports, theses and primary scientific articles) with data on medicinal plants related to the six countries. For this review and in the traditional use context, the terms "blood purifier, blood cleanser, blood detoxifier, blood tonic, blood invigorant or blood strengthener" were used as the search key words in the retrieved reports. Those reports relating to plant usage as tonics (invigorants) and blood thinners, in blood clotting and bloodletting or for treating blood in the stool and blood pressure were excluded as these denoted treatments relating to specific blood diseases (Vuuren and Frank 2020).
Missing information in some studies such as local names and misspelled botanical names was checked from the Google search engine and botanical databases: The Plant List, International Plant Names Index, NCBI taxonomy browser and Tropicos. Most plant names were checked manually in the botanical databases at the point of entry, while the remainder were part of the checked list of ethnomedicinal flora of East Africa (Omara et al. 2021b;Omara 2020a). Another targeted review was undertaken to examine supportive evidences for the potential medical use of the claimed species to discern if scientific explanations could be advanced about their blood purifying, cleansing, detoxifying or strengthening potential.

Causes of sicknesses and the need for blood purification
In East Africa, sicknesses are usually correlated with their possible causes and as such, the medication and posology are contingent on the cause of the disease (Omara 2020b;Chhabra et al. 1984Chhabra et al. , 1993. For life-threatening illnesses or incidences where concerns cite that supernatural forces are behind diseases, diviners may be consulted (Sindiga 1994;Fratkin 1996). Communities attribute illnesses to external polluting influences that interferes with the normal body physiology (impairs digestive and blood circulatory systems) (Fratkin 1996). These may include consuming the "wrong" foods (such as Cheko che makiyo-fresh unboiled milk, dirty water, ikwek-vegetables such as Solanum nigrum and Gynadropis gyandra), introduction of contagious substances from ill people, transgression of a social rule by the victim or a family member. Sometimes, it may also be due to conflicts in relationships between the patient and the spirits, or a violation of witchcraft-related rites and fetishes, and in extreme cases witchcraft (sorcery attacks) (Chhabra et al. 1984;Fratkin 1996;Kaendi 1994;Schlage et al. 2000;Irakiza et al. 2016;Salinitro et al. 2017;Kigenyi 2016). Therefore, determining the origin of an illness is pivotal in the prescription of the appropriate remedy and posology. Traditional treatment regimens are thus meant to relieve intestinal blockages through herbal purgatives and laxatives, or in the case of sorcery, consulting diviners who at their own discretion dispense ritually protective herbal medicines (Fratkin 1996;Salinitro et al. 2017). If evil and ancestral spirits or gods are blamed for the malady, a ritual or ceremony to placate them is arranged. If broken cultural rules or taboos are named as the cause, an act of penance or restitution is prescribed.
In East Africa, blood is considered sacred (Merker 1904;Arhem 1989). For example, when drunk from ritually slaughtered animals among the Maasai of Kenya, it is a sacred food and is symbolically associated with death and rebirth (Arhem 1989). A trial ordeal is reported in which this ethnic group uses blood to prove the innocence of people: a person under trial is made to drink blood under a special curse; if he survives the trial he is declared innocent, if he gets sick or dies he is proven guilty (Arhem 1989;Hollis 1905). Among the Maasai of Tanzania, motorí-a blood-based medicinal soup is commonly consumed with meat and also eaten by the sick. It is typically composed of boiled fat and blood of cows, sheep and goats mixed with medicinal herbs to aid digestion or act as a prophylactic (Roulette et al. 2018). Within the context of traditional medicine, several conditions may induce the need for blood purification, cleansing, detoxification or strengthening (Table 1). However, the plants may also be administered to individuals as a prophylactic or solace therapy during recuperation (Kigen et al. 2017).
In modern medicine however, blood purification is sought as an extracorporeal therapy in extreme cases of renal, hepatic, blood circulatory or immune-inflammatory disease conditions (Thongboonkerd 2010). In this case, blood is taken from a patient's circulation through an extracorporeal circuit; a purification process is applied to it before it is recirculated back into the body. The common purification procedures medically recommended include haemodialysis, hemofiltration, apheresis, autotransfusion and plasmapheresis (Zhou et al. 2013) which adjusts leukocyte recruitment and responsiveness, boosts body immunity, enhances white blood cells' antigen-presenting and phagocytic capability, as well as oxidative burst of immune cells (such as neutrophils and monocytes) (Peng et al. 2010).

Ethnomedicinal plants used in blood purification, cleansing, detoxification and strengthening in East Africa
Allopathic blood purification (and detoxification) is strongly rooted in advanced techniques (involving use of resins, polymers and nanoparticles) which filter out toxic or pathogenic substances from blood (Ju et al. Table 1 Conditions linked with the need for a blood purifier, cleanser, detoxifier or tonic according to East African folk medicine diagnoses Omara Bull Natl Res Cent (2021) 45:171 2019). East African traditional healers, however, connect the use of blood purifiers to their use as rejuvenators (tonics) ( Table 2). Though used for blood purification, these plants are used to treat a range of other diseases and conditions including cancer, venereal diseases, epilepsy, fatigue, fevers, asthma and drug addiction. For example, Rotala tenella (Guill and Per) Hiern is used for management of peripheral neuropathy, muscle cramps, joint pains, pre-and postmenopausal syndromes, lumbago, obesity, cardiovascular/cerebrovascular disorders and hyperlipidaemia other than being used as a blood cleanser. The plant is also popularized among athletes as it is believed to house nutrients that prevent muscle injury (Kigen et al. 2017 (Table 2). Two unidentified plants (Mukururiti and Ruguru) were also reported to be used as blood cleansers in Kenya (Muriuki 2011). The most represented families were Fabaceae (with 7 species), Asteraceae and Rutaceae (4 species each), Amaranthaceae, Meliaceae and Solanaceae with 3 species each. Aloe was the most common genera (represented by 3 species) followed by Acacia, Amaranthus, Dioscorea and Solanum (represented by 2 species each). The Aloe genus is known as a common ingredient of most blood purifier products sold in East Africa (Ugabox 2021;Pigiame 2017).
The herbal remedies are principally prepared as decoctions, chewed, steamed, eaten as a vegetable (e.g. Chenopodium album and Solanum anguivi) or taken as spices in food (e.g. Allium sativum and Persia americana). These remedies are obtained from plant leaves (30.8%), roots (20.6%), bark (12.1%) and fruits (10.3%) (Fig. 1). These are sometimes dried and powdered prior to administration and sometimes mixed with soup, especially for bitter plants (blood tonics). Other recipes included soot from burnt flowers, roots and leaves which are licked. Raw honey (Kumat in native Markweta of Kenya) was also reported to be consumed as a blood cleanser (Kigen et al. 2017).
The relatively frequent use of roots is related to the fact that blood-which is internal to the body-is hidden, just as root structures are hidden in the ground. This gives a correlation to the doctrine of signature concept, i.e. herbs with shape or colour resemblances to body parts could be used to manage ailments of those body parts (Efferth and Greten 2016). Further, a pharmacognostical tenet exists in East African traditional medicine in which red-coloured plants, their parts or herbal preparations cognate with their potential to be used to treat blood-related conditions such as fever, pimples, acne and venereal diseases. For example, a decoction of Vismia orientalis roots is taken as a remedy for lassitude, and because the plant exudes a red gum which resembles blood, it is thought that this can strengthen the blood. Similarly, the sundried and stone-ground Vismia orientalis bark powder is made into a paste with castor oil which is rubbed onto pimples, acne, smallpox, chickenpox or primary syphilis (Kokwaro 1993).
Evidently, there is an East African traditional link between the magical properties of the identified plants and bloodletting, the spilling of blood or connection to spiritual uses (Table 3). This could be because some of the conditions that require blood purification are linked to spiritual causes such as sorcery (Fratkin 1996;Salinitro et al. 2017). In this context, some plants are used to dissuade evil spirits, provide protection against witchcraft, "summon" the rains and other rituals of purification. Similar spiritual linkage of plants used in blood purification has been reported in various communities in Southern Africa (Wyk and Gericke 2000; Moteetee 2017; Maroyi 2011).

Adverse side effects, toxicity and antidotes of the identified plant species
From the reviewed studies, toxicity of plants with reported use as blood purifiers, cleansers, detoxifiers or tonics was not a very common occurrence. However, Aloe species reportedly caused stomach ache, diarrhoea, general body weakness and mild headache (Kamau et al. 2016c). Rhamnus prinoides and Prunus africana had diuretic side effects (Kamau et al. 2016c), while Euclea divinorum and Ricinus communis had purgative and laxative effects (Kamau et al. 2016c;Kigen et al. 2014). From the foregoing, traditional medicine practitioners tended to add animal fats, bovine milk, bone soup or used more than one plant part to neutralize toxic herbal preparations. For example, R. prinoides are used along with Periploca linearifolia, Carissa edulis and Rotheca myricoides, while P. africana could be prepared with Acacia nilotica or Tremma orientalis. About half a glass of Achyranthes aspera leaves and Ficus natalensis (roots) were added to the preparation of Euclea divinorum (Kamau et al. 2016c). However, some practitioners prepare formulations with more than one plant (or plant parts) as a trick of keeping the secrecy of their formula (Kuria et al. 2001). Overall, it should be emphasized that plant toxicity is important in initiating purgation and emesis which are regarded as the key treatment regimen for diseases in Eastern Africa (Omara 2020b;Kaendi 1994;Kiringe 2006). Thus, it is one route of freeing the body of toxins,         Emetic, blood cleanser (Kigen et al. 2017) Antidiabetic (Ojewole 2002), antibacterial, cytotoxic (Tatsimo et al. 2015), anticonvulsant (Makanju 1983;Kenechukwu et al. 2012  Anti-inflammatory, antinociceptive and antipyretic effects (Uzcátegui et al. 2004) Page 14 of 23 Omara Bull Natl Res Cent (2021) 45:171 Fig. 1 Frequency of the reported plant parts used for blood purification, cleansing, detoxification or strengthening in East Africa resulting in blood purification, detoxification, cleansing or strengthening.

Bioactivities of the identified plants
From the reviewed bioactivities of the plants, most investigations were centred on the antimicrobial activity of extracts of the plant parts (upto 65%). This is supported by the reports of ethnobotanical surveys which tended to report the use of the plant parts in treatment of gastrointestinal, dermatological and respiratory ailments ( Table 2). The plausible explanation for this could be the ease and relatively low cost of in vitro antimicrobial testing compared to other reported complex uses of the plants such as treating tuberculosis, HIV/AIDS and malignancies. The current upsurge in antibiotic resistance by genetically versatile microbes could be another explanation (Omara et al. 2021c). Despite the foregoing observation, few studies have investigated bioactivities of the identified species against pathogenic infections (such as tuberculosis, malaria, viral hemorrhagic fever, hepatitis B and C, syphilis and HIV) which are related directly to blood. The most studied plant species (Allium sativum, Basella alba, Centella asiatica, Citrus limon, Clausena anisata, Dioscorea bulbifera, Erythrina abyssinica, Kigelia africana, Lannea schweinfurthii, Moringa oleifera, Nasturtium officinale, Solanum nigrum and Withania somnifera) also have extensive reviews of their various bioactivities (Table 2). However, few of these bioactivities are confirmatory of the supposed use of the plants in purifying, cleansing, detoxifying or strengthening blood and possess little direct positive correlation with (good) blood health. Only 15 (20.2%) species could be correlated with studies pertaining to blood health, for instance, anti-platelet aggregation, vasorelaxant, bronchodilatory, antihyperlipidaemic, cardioprotective and anti-atherosclerotic effects of Allium sativum (Kaur et al. 2016;Sobenin et al. 2019;Silagy and Neil 1994;Bordia et al. 1996;Fehri et al. 2011) andMoringa oleifera (Acuram andHernandez 2019;Aniss et al. 2020;Mehta and Agrawal 2008;Dillasamola et al. 2018;Arabshahi-Delouee et al. 2009;Cáceres et al. 1992;Aekthammarat et al. 2020), antihypertensive and cardioprotective activities of Olea capensis (Susalit et al. 2011;Circosta et al. 1990;Scheffler et al. 2008) and antihypertensive activity of Clausena anisata (Duncan et al. 1999;Lechaba et al. 2016). Cardioprotective activities were also reported for Centella asiatica (Das 2011), Nasturtium officinale (Fogarty et al. 2013), Solanum nigrum (Bhatia et al. 2011) and Withania somnifera (Mohanty et al. 2008), while antihyperlipidaemic and vasorelaxant activities were reported for Rubus apetalus (Raghavendra et al. 2019) and Delonix elata (Ravindra and Priyanka 2018) and Persia americana (Owolabi et al. 2005), respectively. These constitute the first 11 species with notable bioactivities relating to blood health.
Earlier studies among the rural Maasai people of East Africa indicated that they possessed lower blood cholesterol levels compared to those in urban centres and some Europeans, despite their high customary fat diet (Biss et al. 1971a, b;Mann et al. 1964). Day et al. (1976) later suggested that the low serum cholesterol levels of rural Maasai populace could be attributed to their frequent use of medicinal herbs, though the same team never published something more to confirm or reject their assertion. It is hypothesized that the low number of studies focusing on westernized aspects of blood purification, cleansing, detoxification or strengthening potential of the identified plant species could be because this concept from an African perspective is rarely used independently, and possess strong connections with rituals (Table 3) and other religious practices (Cumes 2013;White 2015) that cannot be commingled with modern medicine (Vuuren and Frank 2020).
Other important conditions associated with bad blood health and may be the reason for medicating with a blood purifier (Table 1) such as inappetence and hyperlipidaemia (high serum levels of one or more of total cholesterol, low-density lipoprotein cholesterol, triglycerides or both) have not be investigated for most of the identified species. Evidently, blood purification, cleansing and detoxification procedures in East Africa are strongly correlated with overall human health status. This fact is attested to by the inclusion of parts of common culinary spices, vegetables and food plant species such as Allium sativum (garlic), Amaranthus graeciazans, Amaranthus retroflexus, Beta vulgaris (beetroot), Citrullus lanatus (watermelon), Cleome gynandra, Persia americana (avocado) and Citrus limon (lemon) in the herbal preparations.
Page 16 of 23 Omara Bull Natl Res Cent (2021) 45:171 It is interesting to note that Acacia seyal, Entada abyssinica, Hibiscus acetosella, Lannea schweinfurthii, Parinari curatellifolia and Persia americana were also indicated to be utilized as blood tonics, while Euclea divinorum, Dovyalis abyssinica and Vepris nobilis were indicated as invigorants (tonics). Use of bitter tonics is an old time practice believed to confer beneficial effects on appetite and digestion, through amarum effect, which enhances the flow of saliva, gastric juices via the pneumogastric nervus vagus and the bile (Wyk and Wink 2004;McMullen 2017). Such bitter plant extracts have also been established to exert an effect on the cardiovascular system through reduction of the heart beat rate and cardiac stroke volume (Schulz et al. 2001). Among the species identified in this study, only Withania somnifera (with bitterness values between 2000 and 5000, i.e. moderately bitter) was previously reported to possibly improve digestion and appetite (Olivier and Wyk 2013). Thus, the role of the identified species as tonics in correlation to their claimed use as blood purifiers, cleansers and detoxifiers warrants further probing research. Euclea divinorum Hiern Given to candidates during initiation by the Sebei of Uganda or used in important "koresek" (Sebei) ceremonies (rituals of purification). The root and bark are made into a soup which is taken as a tonic among Sebei of Uganda, Maasai and Batemi of Tanzania Kokwaro 1993;Johns et al. 1999 Kigelia africana Lam Used in rituals, especially against evil spirits. Fruits if applied on a girls' nipples make the breasts grow long, make her ugly and she cannot be married Posthouwer 2015; Hines and Eckman 1993;Kakudidi 2004 Lantana trifolia L Roots and stems used for cleansing and blessing animals. Used in many rituals, including those involving livestock Maundu et al. 2001;Mweru 2018 Lannea schweinfurthii Engl Roots boiled and then the bewitched washes in the water, which is poured out at the nearest road junction

Hines and Eckman 1993
Olea capensis* A sacred tree used during the ceremony of initiating the olorip-olasar (a highly respected young leader among the Maasai of Kenya). The night after his selection, he leans against one of the trees regarded as "peaceful" or "harmless" without flinching Maundu et al. 2001 Osyris lanceolata Treating conditions caused by witchcraft, spirits and magic Schlage et al. 2000 Urtica massaica Mildbr Plants are cut and placed in a sting line of two rows where boys for circumcision run through it several times until their bodies are numb, making them ready for the ritual Amuka et al. 2014 Withania somnifera (L.) Dunal Intestinal parasites introduced by witchcraft Watt and Breyer-Brandwijk 1962 Page 17 of 23 Omara Bull Natl Res Cent (2021) 45:171 Another school of thought in relation to the holistic health effect of the identified species is their potential immunomodulatory properties. Positive immunomodulatory effect has been reported for Allium sativum (Mirabeau and Samson 2012), Aloe vera (Im et al. 2010), Azadirachta indica (Durrani et al. 2008), Centella asiatica (Das 2011), Echinacea angustifolia (Kim et al. 2002), Dioscorea bulbifera (Cui et al. 2016), Moringa oleifera (Li et al. 2020), Nasturtium officinale (Schulze et al. 2021), Persea americana (Bittencourt et al. 2020), Solanum nigrum (Hanifa 2011) and Withania somnifera (Ziauddin et al. 1996;Davis and Kuttan 2000;Chandran and Patwardhan 2017). These constitute the last 4 species with a bioactivity relating to good blood health. Thus, immunomodulatory effect could also be investigated for other species such as Amaranthus graeciazans and Antidesma venosum which were in addition to blood cleansing indicated as immune system boosters. Of the 74 species identified, there were 9 species (12.2%) for which no positive health-related research existed (Table 2). This presents a research gap for future studies on the pharmacological activities of these species.

Conclusions
Blood is considered sacred in East Africa, and ethnomedicinal plants used in blood purification, cleansing, detoxification and strengthening play a revered holistic role. The claimed use of the plants identified could be due to their various biological properties which exert an overall positive effect on human health. However, these bioactivities in most species identified could not be directly correlated with their claimed use in this traditional practice. Further studies should explore blood thinning, hypolipemic, cardioprotective, immunomodulatory, tonic and renoprotective properties of the understudied species. Of the 9 species with no reported bioactivities, Aloe tweediae, Ipomoea lapidosa, Kalanchoe lanceolata, Rotala tenella and Yushania alpine need to be investigated as they have been indicated to be used in the treatment of other conditions directly linked with blood purification, cleansing or detoxification, for example, hyperlipidaemia, obesity, cerebrovascular disorders, viral diseases, paraesthesia, splenomegaly, hepatomegaly, oedema, kidney disorders and inappetence.