preparations is the entire chemical content. It can also be one of the compounds that have confirmed therapeutic activity or a group of compounds with the same core structure and are generally accepted that have a substantial contribution to the drug’s therapeutic activity. With varying chemical contents in a plant, no one plant is recommended for only one disease; and no one disease is related to only one plant [1, 4, 5].
Besides having tremendous potential, various reports show the side effects of herbal products. People always assume that herbal medicines are safe and there are no side effects compared to synthetic drugs due to their nature. This perception causes herbal medicines are often misused and consumed like food, not as medicine. Various studies have shown there are many interactions between herbs with herbs or herbs with drugs. The herbal medicines are considered complementary medicines that can be consumed together with synthetic medicines [6, 7].
Even though herbal medicines lately tend to increase, unfortunately, it is followed by an increase in various adverse effects of herbal use. One of the biggest causes of these cases is closely related to the poor quality of phytopharmaceuticals used. For this reason, the issue of phytopharmaceutical quality is crucial to consider [8].
Difficulties in quality control and lack of scientific evidence in terms of herbal medicines efficacy have resulted in their use being replaced by a synthetic drug. However, in alternative medicine, herbal medicine still exists in various parts of the world [4, 5]. For this reason, the chemical substance composition in phytopharmaceutical has to fulfill the quality because it will influence the effectiveness and safety’s reproducibility at the clinical level [5, 9].
1.2 Common Challenges in Phytopharmaceuticals
Herbal medicines usually consist of plant parts, either single or in combination in pharmaceutical dosage forms. Like synthetic drugs, herbal medicine also has therapeutic or prophylactic properties. The interaction of its multi-component ingredients causes poly-pharmacological effects or is known as a multi-target effect. The application of this concept in phytopharmaceuticals development requires comprehensive characterization of chemical content and bioactivity [10].
Phytopharmaceuticals can become part of the health care system if they can prove their quality to guarantee the safety and efficacy as expected. But until now, it is still challenging to ensure the quality, safety, and effectiveness of phytopharmaceuticals. Quality assurance must be applied at every production stage starting from cultivation, harvesting, post-harvest processing, manufacturing, packaging, and product distribution. Quality assurance at each step is intended to ensure the reproducibility of its effectiveness and safety [5, 9, 11, 12].
Figure 1.1 The great challenges in phytopharmaceuticals reproducibility.
In the following, we will discuss the three most significant challenges of developing phytopharmaceutical products not found in synthetic drugs as illustrated in Figure 1.1.
1.2.1 Authentication of Raw Material
Lately, the use of phytopharmaceuticals has increased so that medicinal plants have become an important agricultural commodity. Many medicinal plants are sold in various dosage forms such as fresh ingredients, dried ingredients, dry powdered materials, and extracts, making it impossible to authenticate morphology because such materials have lost their characteristics. Increased demand for medicinal plants has caused unethical commercial trade, such as replacing authentic raw materials with other materials that are similar but less effective. The act of counterfeiting or mixing herbs of low-quality herbs will affect consumer health and safety, so that authentication and determination of the quality of herbal raw materials is a critical point in guaranteeing the quality of pharmaceuticals [13, 14].
Authentication is a guarantee of compliance with the required specifications. Authentication covers various aspects, including identifying, quantifying of characteristic components, adulteration, contaminants, and verification of quality according to specifications. Specification of medicinal plant raw material is including botanical or geographical origin, manufacturing, or processing procedures of its preparation [15, 16].
Ancient healers have a very high ability to recognize the ingredients used in their medicinal herbs. However, with the development of modernization, the loss of contact with nature has reduced the ability to identify medicinal plants. Ancient texts about herbal medicine are often translated and interpreted differently, and as a result, there are the same names for more than one plant and different names for one plant. This condition is increasingly tricky with language diversity and local dialects [17, 18].
The morphological similarity of plant parts causes misidentification of herbal raw materials. Faulty raw materials can occur either intentionally or unintentionally. Adulteration usually occurs concerning the material’s economic value, for example, by replacing authentic raw material with other similar plant species. Accidental mistakes can happen mainly because workers’ carelessness collects wild plants as raw material [19–21].
Nomenclature problems cause misidentification that often occurs. Local names of plants are often referred to for their traditional use. The local name also often causes mistakes in raw materials and becomes dangerous, especially when replaced by poisonous plants. For example, in Traditional Chinese Medicine (TCM), the name “Fangji” is used for the root of Stephania tetrandra S. Moore (Menispermaceae). This species originated from the northern part of China. The official name in Chinese Pharmacopoeia is “Hanfangji”. The name “Fangji” is also used for the roots of Aristolochiafangchi YC Wu ex LD Chow & SM Hwang (Aristolochiaceae) originating from the southern region. In pharmacopeia, it is referred to as “Guangfangji”, and contains nephrotoxic and carcinogenic acid derivatives [11].
Misidentification also occurs in different species of plants that have the same local name. The two species have different pharmacological activities so that their use will not achieving therapeutic targets. In Indonesia, Mesua ferrea is called “Nagasari”, or in India, it is called “Nagakeshara”, an herb used for heart tonic, cardiotonic, emenagogue, hypotensive, antispasmodic, antianaphylactic, and antiasthmatic. However, Calophyllumino phylum is also sold under the local name “Nagasari” or “Nagakeshara”. This plant is usually used for antiinflammatory and treatment of psoriasis [22, 23].
Hypericum androsaemum is traditionally used for its diuretics and hepatoprotectives. Due to high demand but not in abundant stock, the raw material of H. androsaemum on the market is often found mixed with other genera, which more abundant and cheap or sometimes accidentally mixed with Hypericum perforatum. The traditional medicinal ingredient in China for leg pain and anti-inflammation, Piper kadsura, is often replaced by Piper wallichii. Both species have morphological similarities, but P. waliichii has no medicinal value. The same case also occurs with oriental ginseng (Panax ginseng C.A. Meyer), which is often mixed or replaced with American ginseng (Panax quinquefolius). Traders are forced or deliberately replace the plant parts of the same species or replace them with other species, which have a lower pharmacological or not at all [24–27].
Misidentification cases also occurred in black cohosh plants (Actaea racemosa L., Ranunculaceae). This plant is a raw material for menopause therapy products. This product causes hepatotoxicity in consumers. Valid analysis methods can prove that products on the market do not contain the right plants [21, 28].
In traditional Chinese medicine, Marsdenia tenacissima (Roxb.) Wight et Arn. (Asclepiadaceae) is used to treat esophageal, gastric, lung, and liver cancer. The M. tenacissima is known by the local name as “Tong-guanteng” and is sold in dried, sliced, shredded, and processed forms so that it is often difficult to identify the plant. The M. tenacissima is often replaced with Telosma cordata (Asclepiadaceae) and Fissistigma polyanthum (Annonaceae),